Can a Baby Be Born Addicted to Methadone on a Small Mg

Abstract

Objective:

To compare early growth and developmental issue of infants with in-utero exposure to low-dose methadone (<100 mg per day), loftier-dose methadone (⩾100 mg per day) and buprenorphine.

Study Blueprint:

A retrospective review of infants with in-utero methadone and buprenorphine exposure who were evaluated at the Southcoast Developmental Pediatric dispensary in New Bedford, MA, USA was completed. Growth information and developmental testing results during infancy were compared amongst the groups.

Result:

Infants in the loftier-dose methadone grouping had lower caput circumference z scores and a lower hateful score on the Alberta Infant Motor Scale (AIMS). Regression results confirmed an association betwixt methadone dose and head circumference z score and AIMS score.

Conclusion:

Exposure to maternal methadone dose in excess of 100 mg is associated with a reduction in infant head circumference when compared with buprenorphine or lower dose methadone, and may take a negative impact on motor skill development during early on infancy.

Introduction

Opioid dependence in pregnancy is escalating at an alarming rate in this land. In 2009, three.4 of every 1000 hospital born infants, or ane infant every hour, experienced a narcotic withdrawal.ⁱ In 2013, the number of infants requiring pharmacological treatment for neonatal opiate withdrawal at St Luke's Hospital, a customs hospital in New Bedford, MA, Us was ten times the national average.² Methadone, a full mu-opioid agonist, and buprenorphine, a partial mu-opioid agonist, are 2 maintenance medications offered to pregnant opioid-dependent women.

Previous studies comparison methadone and buprenorphine exposed newborns have focused on the outcome during their hospitalization. McCarthy et al. ^three compared newborns whose mothers were treated with high-dose methadone (⩾100 mg per day) to those whose mothers were treated with low-dose methadone (<100 mg per day) during pregnancy. Results revealed no differences in the rate of medication treatment for neonatal forbearance syndrome (NAS) or days of babe hospitalization between the loftier-dose and depression-dose groups. Schindler et al. ^four found that NAS in neonates born to women treated with buprenorphine appeared to be less severe than the NAS observed in infants of mothers treated with methadone during pregnancy.

Results of the Maternal Opioid Treatment: Homo Experimental Research project, a multicenter randomized, double-blind trial, comparison the outcome of infants with in-utero methadone vs buprenorphine exposure, revealed that, compared with methadone exposed infants, infants prenatally exposed to buprenorphine had a less astringent withdrawal, required significantly less morphine to treat NAS, had a shorter duration of treatment and had a shorter hospital stay.^v A subsequent written report reported that buprenorphine exposed infants exhibited improved neurobehavioral scores when compared with the methadone group during the kickoff month of life.⁶

Brogly et al. ⁷ recently utilized a random-effects meta-assay model to compare prenatal buprenorphine maintenance handling with the methadone maintenance treatment on multiple issue variables. Results revealed buprenorphine maintenance was associated with: lower unadjusted treatment hazard, shorter mean infirmary stay, shorter NAS treatment duration and higher mean gestational historic period, weight, length and caput circumference at birth; moreover, fewer women treated with buprenorphine used illicit opioids almost the time of delivery. They also noted that confounding variables may accept impacted these results.

Although much of the research focus for this population has centered on neonatal outcome and optimizing treatment in the first weeks of life, long-term growth and neurodevelopmental outcomes have been less well studied.

Methods

All newborn infants born at St Luke'south Infirmary with a positive toxicology screen for methadone or buprenorphine were admitted to the Level II Nursery for monitoring. Per protocol, infants were assessed for NAS every 3–4 h by using the Finnegan scoring system, which assesses 21 of the most common signs of neonatal drug withdrawal, including central nervous organisation irritability, respiratory distress and gastrointestinal and autonomic dysfunction. Scoring is based on the pathological significance and severity of the agin symptoms, which sometimes crave a pharmacological treatment.^viii Nursing staff in the St Luke's Level 2 Plant nursery have been trained in using this scoring system, with inter-rater reliability established for several study protocols.^{5, half dozen} Infants with Finnegan scores ⩾viii are treated with medication.⁸ The guideline for treatment included diluted tincture of opium with or without oral phenobarbital from 1995 to 2008, and morphine sulfate with or without oral phenobarbital from 2008 through 2014. When a study research protocol was not in progress, infants were managed per nursery guidelines.

All infants who are discharged from the St Luke's Hospital Level Ii Nursery are scheduled for an cess at the Southcoast Developmental Pediatrics Neonatal Follow-upward program at a mean corrected age of 4 months. The follow-upwardly clinic protocol includes measurement of growth parameters and neurodevelopmental cess completed by a neurodevelopmental pediatrician and an occupational therapist (who is bullheaded to the infant's history).

The infants' anthropometric characteristics were measured using standard techniques. Weight was measured with a Detecto infant scale (Detecto Infant Scales, Brooklyn, NY, Us); length, with an Infantometer (Grafco, Graham Field Surgical, New Hyde Park, NY, USA); and head circumference, with a flexible tape to obtain the largest fronto-occipital circumference. Length and head circumference were recorded to the nearest 0.1 cm. All growth parameters were converted to z scores (distance in s.d. from the hateful) by using the Globe Health Organization Anthropometric reckoner.⁹

A standard neurological examination was completed by a neurodevelopmental pediatrician. Follow-up clinic protocol classifies infants into three categories: normal, no neurological abnormalities; suspect, pocket-sized abnormalities in tone, posture, motion patterns, reflexes, cranial nerves or caput growth; and abnormal, moderate-to-severe abnormalities of tone, posture, movement, asymmetry of reflexes or severe sensory deficits such as blindness or deafness.¹⁰

The Bayley Scales of Infant Evolution was administered to all infants at their follow-upward clinic visit (corrected age 4 months). These scales are the near widely used scales for the evaluation of infant and toddler cognitive development. It has been used routinely in studies examining cerebral outcomes of term and preterm infants using corrected ages. Results were reported equally a Mental Developmental Index, standardized with a mean of 100 and s.d. of 15.¹¹

The Alberta Babe Motor Scale (AIMS) was also administered to all infants at the clinic. The AIMS is a performance-based observational tool for motor cess of infants. A raw score is obtained and converted to a percentile with fifty% being 'average.'¹² Both the Bayley Scales and the AIMS were administered by the aforementioned clinician who was unfamiliar with the infants' medical history.

Between Baronial 1996 and July 2014, 220 infants of mothers treated with methadone or buprenorphine during their pregnancy were evaluated at the Southcoast Developmental Pediatric Follow-up Clinic. A review of the data included in these infants' medical records was completed. Approving was obtained from the Southcoast Hospitals and Boston Children'southward Hospital Research Institutional Review Boards.

Maternal and neonatal characteristics and complications were documented by performing a record review. Maternal data included age, prescription medication and/or illicit substance utilise (per results of history and toxicology screens) during the pregnancy, chronic vs new treatment with methadone or buprenorphine, prenatal intendance and methadone dose. Neonatal information included nascence weight, gestational age, neonatal complications (demand for operative birth, 5-min Apgar score and growth restriction) treatment for NAS, length of hospitalization and foster intendance placement.

Infants were divided into iii groups based on in-utero exposure: maternal methadone dose <100 mg per twenty-four hour period (n=84), maternal methadone dose ⩾100 mg per day (n=81) and maternal buprenorphine (n=55). The methadone groups were divided based on criteria used in previous enquiry.³

Assay of variance and unpaired t-test were used to compare continuous variables, and χ ² was used to compare unimposing variables. Variables included maternal and infant characteristics, growth parameters, the Bayley Scales Mental Developmental Index and the AIMS score. Regression assay was used to examine the association between maternal methadone dose and variables that differed significantly among the groups. Significance level was set at 0.05.

Results

Maternal and infant characteristics are shown in Tabular array i. In that location were no differences in hateful birth weight, gestational age at nascence, gender, maternal age, prenatal care, neonatal complications or infants receiving treatment with phenobarbital.

Table 1 Maternal and infant characteristics

Full size table

Nine mothers in the low-dose methadone group (11%), two mothers in the high-dose methadone group (two%) and xiii infants in the buprenorphine grouping (24%) were begun on treatment with their medication shut to the fourth dimension of their pregnancy (P=0.05). Although results of analysis of variance was non pregnant when comparing the number of infants placed in foster care afterward discharge, farther analysis revealed that a higher percentage of infants in both of the methadone groups were placed into foster care compared to the buprenorphine group.

Results as well revealed that more than mothers who were treated with high-dose methadone were also treated with psychiatric medications (P<0.025); withal, farther analyses betwixt groups revealed that the difference was not significant between the high-dose methadone group and the buprenorphine grouping, both of which had relatively high rates of co-treatment with psychiatric medications. In addition, all three groups differed in their mean length of hospitalization, with the high-dose methadone group hospitalized the longest (44±26 days), followed by the low-dose methadone group (36±22 days), with the buprenorphine exposed infants discharged at a mean of 21±13 days (P<0.001) chronological age. When gestational age at the time of belch was calculated (to correct for prematurity), the departure between the groups remained pregnant: high-dose methadone grouping: 44±v weeks, low-dose methadone grouping: 43±four weeks, buprenorphine grouping: 41±3 weeks (P<0.025).

Growth parameter z scores are shown in Table 2. 3 infants in the low-dose methadone group (3.vi%), vi infants in the high-dose methadone group (7.4%) and two infants in the buprenorphine group (3.6%) did not keep their initial date and were rescheduled; their first visits were therefore completed when they were >7 months of age. Since the mean age at the time of the infants' visits were three.8±2 months for the depression-dose methadone group, iv.9±3 months for the high-dose methadone group and three.9±1 months for the buprenorphine group, comparisons of growth parameter z scores were analyzed instead of the actual measurements. Analysis of variance results revealed meaning differences for the three groups for caput circumference z scores. Furthermore, t-test analysis between groups revealed pregnant differences in head circumference z scores betwixt the high and low-dose methadone groups and betwixt the buprenorphine and high-dose methadone groups.

Table ii Growth parameter z scores

Total size table

Results of the Bayley and AIMS scores are shown in Tabular array 3. In that location was no significant divergence in Bayley Mental Developmental Index scores betwixt the groups. A pregnant difference among the three groups was found in AIMS scores, with the buprenorphine group having a higher score. Results of t-tests revealed a significant difference between the high-dose methadone group and the buprenorphine group.

Table three Bayley and AIMS results

Full size table

Regression analyses were completed examining the clan of length of hospitalization, maternal methadone dose and number of maternal psychiatric medications taken during the pregnancy with head circumference z score and AIMS score. Results revealed that a higher methadone dose and higher number of days of hospitalization were both associated with a lower head circumference z score (R ⁱⁱ=0.127, P<0.001; R ^two=0.103, P<0.001; R ²=0.073, P<0.001), and AIMS score ( and R ²=0.047, P<0.025; R ⁱⁱ=0.047). No associations betwixt number of maternal psychiatric medications taken during the pregnancy and either head circumference z score or AIMS score were found.

Discussion

In this retrospective written report, compared wih infants exposed to low-dose methadone or buprenorphine, infants prenatally exposed to high-dose methadone had smaller head circumference z scores at 3–5 months of age. Previous studies have reported an association between in-utero methadone and buprenorphine exposure and compromised head circumference at birth. Shipton and colleagues reported a 1.2 cm smaller birth head circumference in methadone exposed infants vs salubrious controls at birth,^xiii while Hytinantti et al. ¹⁴ reported below boilerplate head circumference (−0.5 SD) at nativity in buprenorphine exposed infants compared with normative data. Welle-Strand et al. ¹⁵ reported larger caput circumference in buprenorphine exposed infants compared to those newborns exposed to methadone, but results of the Maternal Opioid Handling: Human Experimental Inquiry study did not back up this finding.⁵ In addition, Welle-Strand's grouping institute that although growth parameters at nativity in buprenorphine exposed infants were greater than that seen in the methadone exposed infants, after adjusting for all covariates, simply the head circumference remained significantly different.¹⁵ Data from this current investigation propose that a difference in head circumference may persist beyond the newborn period.

It is notable that the reward of buprenorphine over methadone in this study was most significant when the comparison was made with the high-dose methadone group. It is possible that the issue of buprenorphine, a partial mu-opioid agonist, may exist more like to a lower dose of a full mu-opioid agonist than a higher dose. Moreover, the regression analysis confirmed a dose upshot of methadone exposure to head circumference z scores and AIMS results. Misreckoning variables included length of hospitalization (infants' chronological historic period) and infants' gestational age at the time of belch, which accounts for prematurity. These variables were greater for the infants exposed to high-dose methadone. Furthermore, this group demonstrated a smaller head circumference and lower AIMS score when compared to the other groups.

In beast studies, opiates exhibit effects on the growing brain as reflected in brain size, weight, DNA, RNA and neurotransmitters. Opioids interfere with the GABA system, which can influence the rest of excitatory and inhibitory signals leading to excessive excitation, which can exist a mechanism of prison cell injury and decease.^sixteen Furthermore, prenatal opiate exposure and/or postnatal withdrawal may compromise expression of proteins in neural plasticity.^xvi Yet, examination of the effects of in-utero methadone exposure on neurodevelopmental consequence during infancy has revealed inconsistent results.^{18, xix, 20, 21} Lower amplitude of visual evoked responses have been documented in methadone exposed infants compared to controls,²² and our results reveal a motor advantage in buprenorphine exposed infants compared with infants prenatally exposed to high-dose methadone. Although improved neurodevelopmental scores accept been noted during the neonatal period in buprenorphine compared to methadone exposed neonates,^{half dozen} follow-up studies of methadone and illicit opiate exposed infants and immature children have been confounded by environmental variables. Wilson et al. found that infants prenatally exposed to methadone had lower Bayley Physical Developmental Indices when compared with controls at 9 months of historic period, but no difference in Mental Developmental Index was found. This is like to the difference in AIMS score plant in this study. Multiple studies acknowledge that there are many misreckoning variables such as polydrug use, severity of NAS, neglect of wellness intendance and maternal personality traits that can bear on neurodevelopmental outcome.^{xix, 20, 21} The placement of a college percent of infants with methadone exposure into foster intendance afterward discharge adds another variable to this already very complex network of factors which may impact the neurodevelopmental upshot of these infants. In addition, in our cohort, significantly more than mothers treated with high-dose methadone were likewise treated with psychiatric medications during their pregnancy. Oberlander and colleagues reported that longer gestational exposure to selective serotonin reuptake inhibitors (SSRIs) was shown to be related to lower nativity weight, respiratory distress and reduced gestational age.²³ Farther investigation to explore the specific furnishings of psychiatric medications on infant growth and evolution is needed.

The limitations of this study include its retrospective nature and the inability to control for variables that might impact neurodevelopmental outcome such as degree of withdrawal, maternal smoking, breast feeding and the outpatient environment. The ability to control for all factors effecting outcome is very challenging and ofttimes times not applied for this population. Nonetheless, this is an at gamble group of patients, the numbers of which are escalating at an alarming charge per unit and as such warrant continued written report.

We conclude that when compared to maternal buprenorphine or lower dose methadone, exposure to maternal methadone doses in excess of 100 mg is associated with a reduction in infant caput circumference and when compared with maternal buprenorphine exposure, has a negative impact on motor skill evolution during early infancy. This retrospective report provides further evidence that maternal drug and dose exposure to the fetus may play a role in early on growth and motor evolution.

References

1. Patrick SW, Schumacher RE, Benneyworth BD, Krans EE, McAllister JM, Davis MM . Neonatal forbearance syndrome and associated health care expenditures United States, 2000-2009. JAMA 2012; 307 (18): 1934–1940.

   CAS  Commodity  Google Scholar

2. Coyle MG Unpublished data from presentation, "Do newborns really care what drug their mother took?", Neonatal Abstinence Syndrome Statewide Improvement Projection, Neonatal Quality Improvement Collaborative of Massachusetts: Westborough, MA, 13/vi/13.

3. McCarthy JJ, Leamon MH, Parr MS, Anania B . High-dose methadone maintenance in pregnancy: maternal and neonatal outcomes. Am J Obstet Gynecol 2005; 193 (3Pt1): 606–610.

   CAS  Article  Google Scholar

4. Schindler SD, Eder H, Ortner R, Rhrmeister K, Langer Thousand, Fischer G . Neonatal outcome following buprenorphine maintenance during conception and throughout pregnancy. Addiction 2003; 98 (i): 103–110.

   Commodity  Google Scholar

5. Jones HE, Kaltenbach One thousand, Heil SH, Stine SM, Coyle MG, Arria AM, O'Grady KE, Selby P, Martin PR, Fischer G . Neonatal abstinence syndrome afterward methadone or buprenorphine exposure. Due north Engl J Med 2010; 363 (24): 2320–2331.

   CAS  Commodity  Google Scholar

6. Coyle MG, Salibury AL, Lester BM, Jones HE, Lin H, Graf-Rohrmeister M, Fischer G . Neonatal neurobehavior effects following buprenorphine versus methadone exposure. Addiction 2012; 107 (Suppl.1): 63–73.

   Article  Google Scholar

7. Brogly SB, Saia KA, Walley AY, Du HM, Sebastiani P . Prenatal buprenorphine versus methadone explosure and neonatal coutcomes: systematic review and meta-analysis. Am J Epidemiol 2014; 180 (7): 673–686.

   Commodity  Google Scholar

8. Finnegan LP, Kaltenbach K et al. Neonatal abstinence syndrome In: Hoekelman FA, Friedman SB, Nelson NM (eds). Chief Pediatric Care 2. Mosby: St Louis, MO, 1992; 1367–1378.

   Google Scholar

9. WHO Anthro for personal computers, version 3.2.2, 2011: Software for assessing growth and development of the globe's children. Geneva: WHO 2010, http://www.who.int/childgrowth/software/en/.

10. Vohr BR, Garcia-Coll C . Neurodevelopmental and school operation of very low nascency weight infants: a 7-year longitudinal study. Pediatrics 1985; 176: 345–350.

    Google Scholar

11. Bayley Scales of Babe Development. 2nd edn. Psychological Corporation: New York, NY, 1993.

12. Piper MC, Darrah J . Motor Assessment of the Developing Baby. WB Saunders Company: Philadelphia, PA, 1994.

    Google Scholar

13. Shipton D, Mactier H, Dryden C, Tappin D . Substitute methadone prescribing in pregnancy is associated with dumb fetal head growth. Arch Dis Kid Fetal Neonatal Ed 2011; 96: Fa45.

    Article  Google Scholar

14. Hytinantti T, Kahila H, Renlund 1000, Jarvenpaa A, Halmesmaki East, Kivitie-Kallio Due south . Neonatal upshot of 58 infants exposed to maternal buprenorphine in utero. Acta Paediatr 2008; 97: 1040–1044.

    CAS  Article  Google Scholar

15. Welle-Strand G, Skurtveit S, Jones H, Waal H, Bakstad B, Bjarkø L, Ravndal E . Neonatal outcomes following in utero exposure to methadone or buprenorphine: A National Cohort Study of opioid-agonist treatment of Significant Women in Norway from 1996 to 2009. Drug Alcohol Depend 2013; 127: 200–206.

    CAS  Article  Google Scholar

16. Lui A, Bjorkman T, Stewart C, Nanan R . Pharmacological treatment of neonatal opiate withdrawal: betwixt the devil and the deep blueish bounding main. Int J Pediatr 2011; 2011: 935631.1–935631.5.

    Google Scholar

17. Schrott LM, Franklin LM, Serrano PA . Prenatal opiate exposure impairs radial arm maze performance and reduces levels of BDNF precursor following grooming. Brain Res 2008; 1198: 132–140.

    CAS  Article  Google Scholar

18. McCarthy JJ, Leamon MH, Parr MS, Anania B . High-dose methadone maintenance in pregnancy: maternal and neonatal outcomes. Am J Obst Gyn 2005; 193 (3Pt1): 606–610.

    CAS  Article  Google Scholar

19. Wilson GS, Desmond MM, Wlit RB . Follow-up of methadone-treated women and their infants: Wellness, development, and social implications. J Pediatr 1981; 98: 716–722.

    CAS  Article  Google Scholar

20. Kronstadt D . Complex developmental problems of prenatal drug exposure. Drug Exposed Infants 1 (1) 1991.

21. Kaltenbach Thou, Finnegan L . Developmental outcome of children born to methadone maintained women: a review of longitudinal studies. Neurobehav Toxicol Teratol 1984; vi: 271–275.

    CAS  PubMed  Google Scholar

22. McGlone 50, Mactier H, Hamilton R, Bradnam MS, Boulton RG, Borland W, Hepburn One thousand, McCulloch DL . Visual evoked potentials in infants exposed to methadone in utero. Arch Dis Child 2008; 93 (ix): 784–786.

    CAS  Commodity  Google Scholar

23. Oberlander TF, Misri S, Fitzgerald CE, Kostaras Ten, Rurak D, Riggs W . Pharmacologic factors associated with transient neonatal symptoms following prenatal psychotropic medication exposure. J Clin Psychiatry 2004; 65: 230–237.

    CAS  Article  Google Scholar

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Affiliations

1. Section of General Pediatrics, Boston Children's Infirmary, Harvard Medical School, Boston, MA, USA

   J B Bier

2. Department of Orthopaedic Surgery, Massachusetts Full general Hospital, Harvard Medical School, Boston, MA, USA

   A S Finger

3. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical Schoolhouse, Boston, MA, U.s.

   B A Bier

4. Department of Physical Medicine, St Luke's Hospital, New Bedford, MA, The states

   T A Johnson & Grand Chiliad Coyle

5. Department of Pediatrics, Women & Infants' Hospital, Warren Alpert Medical School of Brownish University, Providence, RI, USA

   Yard G Coyle

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Correspondence to J B Bier.

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The authors declare no conflict of interest.

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Bier, J., Finger, A., Bier, B. et al. Growth and developmental outcome of infants with in-utero exposure to methadone vs buprenorphine. J Perinatol 35, 656–659 (2015). https://doi.org/10.1038/jp.2015.22

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• Received: 08 Nov 2014

• Revised: 22 February 2015

• Accepted: 23 February 2015

• Published: 02 April 2015

• Issue Engagement: Baronial 2015

• DOI : https://doi.org/x.1038/jp.2015.22

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