Assignment 3: Literature Review: Five Articles Abstracted onto the Evaluation TableIn Weeks 2–7, you will submit an evaluation table document with five research articles abstracted for your literatu
4/26/2018 Methadone and buprenorphine for opioid dependence during pregnancy: A retrospective cohort study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375023/ 1/11
G o to :
G o to :
J A ddic t M ed . A uth or m anuscrip t; a va ila ble in P M C 2 016 M ar 1 .
P ublis h ed in fin al e dit e d fo rm a s:
J A ddic t M ed. 2 015 M ar-A pr; 9 (2 ): 8 1–86.
doi: 1 0.1 097/A D M .0 000000000000092
P M CID : P M C4375023
N IH M SID : N IH M S635993
P M ID : 2 5622120
M eth adone a nd b upre norp hin e fo r o pio id d ependence d urin g p re gnancy: A
r e tr o sp ectiv e c o hort s tu dy
Marjo rie C . M eye r , M .D ., A nne M . J o hnsto n , M .D ., A big ail M . C ro cke r , P h.D ., a nd S ara h H . H eil , P h.D .
Marjo rie C . M eye r, D epartm ent o f O bste tr ic s, G yn eco lo gy & R epro ductiv e S cie nce s, U niv e rs it y o f V erm on t, B urlin gto n, V T, U nit e d
S ta te s.
C ontr ib uto r In fo rm atio n .
C orre sp ondin g a u th or : M arjo rie C . M eye r, M .D ., S m it h 4 19, M CHV C am pus, 1 11 C olc h e ste r A ve n ue, B urlin gto n, V T 0 5401, P ho ne:
802-8 74-4 797, F A X: 8 02-8 47-2 772, M arjo rie .M eye r@ uvm .e du
C opyrig ht n otic e
T he p ublis h er's fin al e dit e d v e rs io n o f th is a rtic le is a va ila ble a t J A ddic t M ed
S ee o th er a rtic le s in P M C th at c it e th e p ublis h ed a rtic le .
A bstr a ct
O bje ctiv e
T o c o m pare m ate rn al c h ara cte ris tic s, p re n ata l c are a n d n ew born o utc o m es i n a c o hort o f o pio id -
dep en den t p re g nan t w om en t r e ate d w ith m eth ad one v s. b upre n orp hin e.
M eth ods
R etr o sp ectiv e c o hort s tu dy. 6 09 p re g nan t, o pio id -d ep en den t w om en w ere t r e ate d w ith m eth ad one
(n = 248) o r b upre n orp hin e ( n = 361) b etw een 2 000–2012 a t a s in gle i n stitu tio n.
R esu lt s
M oth ers t r e ate d w ith b upre n orp hin e w ere m ore l ik ely t o s ta rt m ed ic atio n p rio r t o o r e arlie r i n
p re g nan cy, h ad l o nger g esta tio n a n d l a rg er i n fa n ts . N ew born s o f b upre n orp hin e- v s. m eth ad one-
m ain ta in ed m oth ers r e q uir e d t r e atm en t f o r n eo nata l a b stin en ce s ig nif ic an tly l e ss o fte n a n d f o r a s h orte r
d ura tio n.
C onclu sio ns
T hese d ata s u ggest p re g nan cy o utc o m es f o llo w in g b upre n orp hin e t o t r e at o pio id d ep en den ce d urin g
pre g nan cy i n c lin ic al p ra ctic e a re a s g oo d a n d o fte n b ette r t h an o utc o m es w ith m eth ad one. T hese
re su lts a re c o nsis te n t w ith e ff ic acy d ata f ro m r a n dom iz ed c lin ic al t r ia ls a n d f u rth er s u pport t h e u se o f
bupre n orp hin e f o r t h e t r e atm en t o f o pio id -d ep en den ce d urin g p re g nan cy.
K ey w ord s: p re g nan cy, o pio id d ep en den ce, b upre n orp hin e, m eth ad one
IN TR O DUCTIO N 4/26/2018 Methadone and buprenorphine for opioid dependence during pregnancy: A retrospective cohort study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375023/ 2/11
G o to :
O pio id d ep en den ce d urin g p re g nan cy i s o fte n c o m pounded b y m ultip le r is k f a cto rs c o ntr ib utin g t o
a d vers e m ate rn al a n d n ew born c o nse q uen ces ( K an dall e t a l 1 977 ; L if s c h itz e t a l 1 985 ; H uls e e t a l
1 997 ; L este r e t a l, 2 004 ; M essin ger e t a l 2 004 ; W in klb au r e t a l 2 008 ). F or o ver f o ur d ecad es
m eth ad one h as b een t h e r e co m men ded s ta n dard o f c are f o r t r e atin g o pio id -d ep en den t p re g nan t p atie n ts .
In t h e c o nte x t o f c o m pre h en siv e c are , m eth ad one m ain te n an ce i m pro ves m ate rn al a n d n ew born
o utc o m es r e la tiv e t o n o t r e atm en t o r m ed ic atio n-a ssis te d -w ith dra w al ( K alte n bach e t a l, 1 998 , J o nes e t
al 2 008 , W in klb au r e t a l 2 008 ).
D esp ite n um ero us s m all s tu die s t h at h av e e x am in ed t h e s a fe ty a n d e ff ic acy o f b upre n orp hin e f o r t h e
tr e atm en t o f o pio id d ep en den ce d urin g p re g nan cy ( J o nes e t a l 2 012 ), o nly a f e w s tu die s c o m pare d
tr e atm en t w ith m eth ad one t o b upre n orp h in e ( J o nes e t a l 2 005 ; F is c h er e t a l 2 006 ; L eje u ne e t a l 2 006 ;
B in der e t a l 2 008 ; K ak ko 2 008 ; B ak sta d e t a l 2 009 ; J o nes e t a l 2 010 ; L acro ix 2 011 ). M ost d ata s u ggest
th at n ew born s e x pose d t o b upre n orp hin e in u te ro d em onstr a te m ild er, m ore l im ite d n eo nata l a b stin en ce
sy m pto m s c o m pare d t o m eth ad one. T he m ost r ig oro us c o m paris o n c o nducte d w as t h e M OTH ER s tu dy,
a m ulti- s ite r a n dom iz ed c o ntr o lle d t r ia l i n w hic h m ate rn al p artic ip an ts r e ceiv ed s tu dy m ed ic atio n i n a
d ouble -b lin d, d ouble -d um my m an ner ( J o nes e t a l 2 010 ). T he r ig oro us t r ia l r e q uir e m en ts o f t h e
M OTH ER s tu dy s p ecif ic ally a d dre sse d t h e e ff ic acy o f b upre n orp hin e v ers u s m eth ad one f o r t h e
tr e atm en t o f o pio id d ep en den ce d urin g p re g nan cy.
In e v ery day p ra ctic e, h ow ev er, t r e atm en t a llo catio n i s n ot r a n dom iz ed . D ev elo pm en t o f a t r e atm en t
pla n f o r s u bsta n ce a b use i n clu des a d dre ss in g m yria d o f s o cia l f a cto rs , i n clu din g h ousin g, f a m ily d ru g
use , a n d o fte n p rio r t r e atm en t f a ilu re s. I n t h is r e g ard , t h e t ig htly c o ntr o lle d e n vir o nm en t o f r a n dom iz ed
tr ia ls m ay n ot p ro vid e s u ff ic ie n t i n fo rm atio n f o r g en era l u se .
T he g oal o f t h is s tu dy i s t o c o m pare m ate rn al c h ara cte ris tic s, p re n ata l c are a n d n ew born o utc o m es i n
w om en t r e ate d w ith b upre n orp hin e v ers u s m eth ad one f o r o pio id -d ep en den ce d urin g p re g nan cy i n a
s e ttin g i n w hic h t r e atm en t a llo catio n w as c lin ic ally d ete rm in ed . T o o ur k now le d ge, t h is i s t h e l a rg est
stu dy t o d ate c o m parin g t h e e ff e ctiv en ess o f t h ese t w o o pio id a g onis t t h era p ie s ( O AT) d urin g
pre g nan cy a s p re sc rib ed i n c lin ic al p ra ctic e.
M ETH O DS
Partic ip ants
S tu dy s u bje cts w ere i d en tif ie d r e tr o sp ectiv ely f ro m a d ata b ase o f n ew born s w ith a k now n in u te ro
o pio id e x posu re m ain ta in ed f o r q uality a ssu ra n ce p urp ose s. A t o ta l o f 8 06 m oth er- n ew born d yad s w ere
id en tif ie d i n t h e d ata b ase f o r p ote n tia l s tu dy i n clu sio n. M oth er- n ew born d yad s w ere e x clu ded f ro m t h e
stu dy i f t h e m oth er w as t r e ate d w ith a n O AT f o r r e aso ns o th er t h an o pio id d ep en den ce ( n = 47), t h e
m oth er w as t r e ate d a s p art o f t h e M OTH ER s tu dy ( n = 25), t h e m oth er h ad a k now n o pio id d ep en den ce
b ut w as n ot p re sc rib ed a n O AT ( n = 78), t h e m oth er d eliv ere d a t a n o uts id e i n stitu tio n ( n = 40), o r t h e
new born h ad a n A PG AR s c o re o f 0 ( n = 7). 6 09 m oth er- n ew born d yad s t r e ate d f o r o pio id d ep en den ce
d urin g p re g nan cy w ith m eth ad one o r b up re n orp hin e a n d d eliv ere d a t a s in gle i n stitu tio n b etw een
A ugust 2 000–Ju ne 2 012 w ere i n clu ded i n t h is s tu dy. T he s tu dy w as r e v ie w ed a n d a p pro ved b y t h e
C om mitte es o n H um an R ese arc h a t t h e U niv ers ity o f V erm ont.
O bste tr ic c a re
W om en w ere t r e ate d a t t h e t e rtia ry c are o bste tr ic c lin ic w ith a n o n-s ite s o cia l w ork er a n d a s in gle
p ro vid er f o r b oth o bste tr ic s a n d b upre n orp hin e m ain te n an ce o r a t c o m munity o bste tr ic p ra ctic es.
U ltr a so und f o r v ia b ility w as p erfo rm ed b efo re i n itia tio n o f m ed ic atio n f o r o pio id d ep en den ce.
S ubse q uen tly , r o utin e p re n ata l c are w as p ro vid ed . D ecis io ns r e g ard in g p re g nan cy m an ag em en t,
a n alg esia , t im in g a n d m ode o f d eliv ery , a n d p ostp artu m c are w ere p er s ta n dard o bste tr ic p ra ctic e. F or 4/26/2018 Methadone and buprenorphine for opioid dependence during pregnancy: A retrospective cohort study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375023/ 3/11
m oth ers w ho w ere n ot o n O AT a t t im e o f c o ncep tio n, e stim ate d g esta tio nal a g e ( E G A ) a t i n itia tio n o f
tr e atm en t w as r e co rd ed .
N ew born o utc o m es i n clu ded g en der ( m ale /f e m ale ), E G A a t d eliv ery , p re te rm d eliv ery ( E G A l e ss t h an
3 7 w eek s), b ir th w eig ht i n g ra m s, b ir th w eig ht s ta n dard iz ed f o r g en der a n d E G A ( z -s c o re ), b ir th w eig ht
le ss t h an 5 p erc en tile ( y es/n o), h ead c ir c u m fe re n ce i n c en tim ete rs , h ead c ir c u m fe re n ce s ta n dard iz ed
fo r g en der a n d E G A ( z -s c o re ), n on-p re te rm n ew born l e n gth o f h osp ita l s ta y i n d ay s, n ew born r e ceiv in g
an y b re ast m ilk a t d is c h arg e ( y es/n o) a n d i f t h e n ew born w as d is c h arg ed i n t h e c are o f t h e m oth er o r
fa m ily ( y es/n o). I n a d ditio n, n ew born s w ere c la ssif ie d a s n eo nata l a b stin en ce s y ndro m e ( N A S) p ositiv e
if t h e n ew born r e q uir e d p harm aco lo gic t r e atm en t f o r w ith dra w al s y m pto m s. F or N AS p ositiv e
new born s, N AS t r e atm en t d ura tio n i n d ay s w as a ls o m easu re d .
O pio id m edic a tio n m anagem ent
O pio id a g onis t t h era p y m ed ic atio n m an ag em en t w as d ete rm in ed b y i n div id ual a sse ssm en t, w hic h
in clu ded s u ccess w ith p rio r o r o ngoin g t r e atm en t, t r e atm en t a v aila b ility , a cu ity , t r a n sp orta tio n n eed s,
a n d p atie n t c h oic e ( S A M HSA , 2 004 ). P re g nan t w om en w ith out i n su ra n ce w ere e lig ib le f o r M ed ic aid ,
w hic h c o vere d e ith er m ed ic atio n o ver t h e c o urs e o f t h e p re g nan cy. I n g en era l, w om en t h at c o nceiv ed
w hile p artic ip atin g s u ccessfu lly i n a n o pio id m ain te n an ce p ro gra m w ere m ain ta in ed o n t h at m ed ic atio n
th ro ughout p re g nan cy. A ll w ere i n fo rm ed t h at m eth ad one w as t h e t r e atm en t o f c h oic e d urin g
pre g nan cy a n d o ff e re d a m ed ic atio n c h an g e i f d esir e d . F or t h ose i n b upre n orp hin e t r e atm en t,
m onoth era p y ( i.e ., S ubute x ) w as p re sc rib ed o nce p re g nan cy v ia b ility w as e sta b lis h ed .
P re g nan t w om en s e lf -re p ortin g o pio id d ep en den ce ( re g ula r u se o f a n o pio id a g onis t w ith w ith dra w al
sy m pto m s u pon c essa tio n) b ut n ot r e ceiv in g t r e atm en t w ere o ff e re d m ed ic al s o cia l w ork a sse ssm en t
an d a d m is sio n t o c o nfir m p hysic al d ep en den ce o n o pio id s. M ed ic atio n a ssis te d t h era p y w as i n itia te d i n
t h e h osp ita l s e ttin g o ver 2 4–36 h ours , w ith r e g ula r a sse ssm en t f o r s ig ns o f o pio id w ith dra w al u sin g t h e
C lin ic al I n stitu te N arc o tic A sse ssm en t ( C IN A) s c ale ( P each y e t a l, 1 988) a n d m ed ic atio n i n itia te d
w hen m ild -m odera te s y m pto m s w ere o bse rv ed ( s c o re o f 1 0). M ed ic atio n w as i n itia te d a t a l o w d ose
(m eth ad one 1 0 m g t o m ax im um 3 0 m g i n 2 4 h ours ; b upre n orp hin e ( i.e ., S ubute x ) 2 m g t o m ax im um 4
m g i n 2 4 h ours ) b ase d o n s y m pto m r e lie f; o n r a re o ccasio ns, h ig her d ose s w ere u se d f o r s e v ere
s y m pto m s. A fte r i n itia tio n, p atie n ts w ere d is c h arg ed a n d s e en e v ery 2 4 h ours ( m eth ad one) o r 2 4–72
hours ( b upre n orp hin e) u ntil d ose w as s ta b le a n d w ith dra w al s y m pto m s i m pro ved .
M eth ad one w as t h e o nly m ed ic atio n i n iti a te d d urin g p re g nan cy u ntil 2 004, w hen u se o f b upre n orp hin e
beg an . B upre n orp hin e u se i n cre ase d o ver t im e u ntil 2 008, a t w hic h t im e t h e r a te s o f u se o f m eth ad one
an d b upre n orp hin e s ta b iliz ed . A fte r i n iti a tio n, m eth ad one m ain te n an ce w as i n itia lly p ro vid ed t h ro ugh
th e p harm acy ( n = 34) a n d l a te r a t a n o pio id t r e atm en t c en te r ( n = 193; m is sin g d ata n = 21). I n e ach
se ttin g, m eth ad one w as a d m in is te re d d aily . M oth ers t r e ate d t h ro ugh t h e p harm acy w ere r e fe rre d f o r
co unse lin g i n t h e c o m munity . M oth ers t r e ate d a t t h e o pio id t r e atm en t p ro gra m h ad c o unse lin g a n d
m en ta l h ealth a sse ssm en t w ith in t h e p ro gra m . B upre n orp hin e m ain te n an ce w as p ro vid ed b y a n
o bste tr ic p ro vid er ( n = 190), a t r e atm en t c en te r ( n = 24), o r c o m munity p ro vid er ( n = 134) ( u ndocu m en te d ,
n= 13). C ounse lin g w as r e co m men ded t o a ll w om en r e ceiv in g b upre n orp hin e, w ith s o cia l w ork v is its t o
a ssis t i n c o ord in atio n.
A fte r i n itia l s ta b iliz atio n o n s e le cte d m ed ic atio n, t h e m ed ic atio n d ose w as i n cre ase d i n cre m en ta lly
d urin g p re g nan cy b ase d o n r e p orte d w ith d ra w al s y m pto m s a n d c lin ic al a sse ssm en t. U rin e d ru g s c re en s
w ere p erfo rm ed w eek ly a t t h e p la ce o f t h e o pio id a g onis t m ed ic atio n p ro vid er a n d u se d f o r c lin ic al
d ecis io n-m ak in g b ut w ere n ot a v aila b le f o r a n aly sis . O nce m ed ic atio n w as i n itia te d , t h ere w as n o
m ed ic atio n c h an ge w ith out a s p ecif ic i n dic atio n. D urin g h osp ita liz atio n f o r d eliv ery a n d p ostp artu m ,
wom en r e m ain ed o n t h eir o pio id m ain te n an ce t h era p y.
th 4/26/2018 Methadone and buprenorphine for opioid dependence during pregnancy: A retrospective cohort study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375023/ 4/11
G o to :
N ew born c a re
A ll m oth ers r e ceiv in g O AT w ere r e fe rre d t o t h e N eo nata l M ed ic al F ollo w -u p C lin ic d urin g p re g nan cy
fo r c o nsu lta tio n. U pon d eliv ery , n ew born s w ere h osp ita liz ed f o r a sse ssm en t o f N A S. B re astf e ed in g w as
e n co ura g ed , e x cep t f o r w om en a ctiv ely u sin g c o cain e ( n o p atie n ts w ere H IV p ositiv e). W hile
h osp ita liz ed , N AS a sse ssm en ts w ere c o nducte d e v ery 3 –4 h ours f o r a t l e ast t h e f ir s t 4 d ay s p ostn ata l
(9 6h) u sin g a 1 9-ite m m odif ie d F in neg an S cale ( J a n sso n, 2 009 ). P harm aco lo gic t r e atm en t f o r t w o
co nse cu tiv e t o ta l s c o re s ≥ 9 o r o ne s c o re > 1 3. T he m ajo rity o f n ew born s r e q uir in g p harm aco lo gic al
tr e atm en t f o r n eo nata l a b stin en ce s y m pto m s a t o ur u niv ers ity -a ff ilia te d h osp ita l a re t r e ate d i n a n
o utp atie n t s e ttin g u sin g m eth ad one, o nce s ta b iliz ed i n t h e i n patie n t s e ttin g.
V aria ble s
T he 6 09 m oth er- n ew born d yad s i n clu ded i n t h e s tu dy w ere c la ssif ie d a s e ith er m eth ad one o r
bupre n orp hin e a cco rd in g t o t h e m oth er’s O AT t y pe a t d eliv ery . V aria b le s r e g ard in g m ate rn al
c h ara cte ris tic s, p re n ata l c are a n d n ew born o utc o m es w ere m easu re d a n d c o m pare d f o r t h ese t w o s tu dy
gro ups.
M ate rn al c h ara cte ris tic s i n clu ded a g e a t d eliv ery ( in y ears ), h ep atitis C p ositiv e ( y es/n o), n ullip aro us
(y es/n o), s m okin g d urin g p re g nan cy ( y es/n o) a n d n um ber o f c ig are tte s s m oked p er d ay d urin g t h ir d
tr im este r.
P re n ata l c are c h ara cte ris tic s i n clu ded e stim ate d g esta tio nal a g e ( E G A) i n w eek s a t i n itia l p re n ata l c are
v is it, p re n ata l c are i n itia te d i n f ir s t t r im este r ( y es/n o), a d eq uate p re n ata l c are r e ceiv ed ( y es/n o)
acco rd in g t o K ote lc h uck i n dex ( K ote lc h uck e t a l, 1 994 ), m ate rn al b ody m ass i n dex ( B M I) a t i n itia l
p re n ata l c are v is it, m ate rn al w eig ht c h an ge i n p ounds d urin g p re g nan cy, d eliv ery m eth od ( c esa re an -
se ctio n v s. o th er). I n fo rm atio n r e g ard in g O AT i n itia tio n w as m easu re d , c ate g oriz in g i n itia tio n a s p rio r
to c o ncep tio n ( y es/n o).
S ta tis tic a l a naly sis
A ll a n aly se s w ere c o nducte d u sin g S ta ta 1 2.0 ( S ta tC orp . C olle g e s ta tio n, T X ). D esc rip tiv e s ta tis tic s
w ere u se d t o d esc rib e t h e c h ara cte ris tic s o f t h e m oth er- n ew born d yad s i n clu ded i n t h e s tu dy c o hort.
B oth p ara m etr ic a n d n on-p ara m etr ic u niv aria te a n aly se s w ere p erfo rm ed t o i d en tif y s ig nif ic an t
dif f e re n ces ( P < 0.0 5) b etw een t h e m eth ad one a n d b upre n orp hin e t r e ate d g ro ups. A dditio nal m ultiv aria te
a n aly se s w ere c o nducte d u sin g v aria b le s t h at w ere i d en tif ie d a s s ig nif ic an t i n t h e u niv aria te a n aly se s t o
d ete rm in e i f t h ey r e m ain ed s ig nif ic an t i n t h e m ultiv aria te s e ttin g.
R ESU LT S
This s tu dy i n clu ded 6 09 m oth er- n ew born d yad s t r e ate d f o r o pio id -d ep en den ce d urin g p re g nan cy u sin g
m eth ad one o r b upre n orp hin e. T he d is tr ib utio n o f w om en o n O AT a t d eliv ery a n d t r e atm en t f ro m 2 000–
2012 a re r e fle cte d i n F ig ure 1 . M ate rn al c h ara cte ris tic s a re o utlin ed i n T ab le 1 . N ullip aro us m oth ers
w ere m ore o fte n t r e ate d w ith b upre n orp hin e; h ep atitis C w as m ore p re v ale n t i n m oth ers t r e ate d w ith
m eth ad one. T he p re v ale n ce o f s m okin g w as g re ate r t h an 8 0% i n b oth g ro ups. D if f e re n ces i n n ullip arity
a n d h ep atitis C s ta tu s r e m ain ed s ig nif ic an t i n t h e m ultiv aria te a n aly sis c o ntr o llin g f o r y ear o f b ir th ,
m ate rn al a g e a n d s m okin g d urin g p re g nan cy. 4/26/2018 Methadone and buprenorphine for opioid dependence during pregnancy: A retrospective cohort study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375023/ 5/11
F ig ure 1
D is tr ib utio n o f w om en t r e a te d w it h m eth ad on e o r b upre n orp hin e d urin g p re g n an cy f r o m A ugu st
2 000–Ju ne 2 012
A : P erc en t o f w om en r e ceiv in g o pia te a g onis t t h era p y p rio r t o p re g nan cy. T he o pen b ar r e p re se n ts w om en
tr e ate d w ith m eth ad one ( n = 95/2 25 ( 3 9.7 % )); t h e h atc h ed b ar r e p re se n ts w om en t r e ate d w ith b upre n orp hin e
(n = 196/3 42 ( 6 0.3 % )). B : G esta tio nal a g e a t w hic h o pia te a g onis t t h era p y w as i n itia te d i n w om en s ta rtin g
tr e atm en t d urin g p re g nan cy ; c ir c le s r e p re se n t t h e m ean g esta tio nal a g e ( w eek s) a n d l in es r e p re se n t t h e
sta n dard d ev ia tio n. T he o pen c ir c le r e p re se n ts w om en t r e ate d w ith m eth ad one ( n = 12 4: 1 8.9 ± 9.1 w eek s;
n = 6 m is sin g d ata ); t h e h atc h ed c ir c le r e p re se n ts w om en t r e ate d w ith b upre n orp hin e ( n = 13 7: 1 5.9 ± 8.1
w eek s; n = 9 m is sin g d ata ).
T a ble 1
M ate rn al C hara cte ris tic s
M eth ad on e
(N =248)
B upre n orp hin e
(N =361) P
N m ( s d ) o r n ( % ) N m ( s d ) o r n ( % )
Age a t d eliv ery ( y ears ) 2 48 26.3 ( 4 .5 ) 361 26.0 ( 4 .0 ) .4 56
H ep atitis C p ositiv e 245 100 ( 4 1% ) 343 88 ( 2 6% ) <.0 01
N ullip aro us 248 58 ( 2 3% ) 361 131 ( 3 6% ) .0 01
S m oker, d urin g p re g nan cy 2 11 1 84 ( 8 7% ) 353 292 ( 8 3% ) .1 56
3 t r im este r, n um ber o f c ig are tte s p er d ay 2 11 1 0.0 ( 9 .3 ) 353 8.6 ( 9 .0 ) .0 85 rd 4/26/2018 Methadone and buprenorphine for opioid dependence during pregnancy: A retrospective cohort study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375023/ 6/11
m , M ean ; s d , S ta n dard D ev ia tio n
In dic es o f p re n ata l c are a re p re se n te d i n T ab le 2 ; e n tr y i n to p re n ata l c are w as s im ila r b etw een t h e t w o
gro ups w ith m ore t h an 6 5% o f m oth ers i n itia tin g p re n ata l c are i n t h e f ir s t t r im este r. M oth ers t r e ate d
w ith b upre n orp hin e w ere m ore l ik ely t o r e ceiv e a d eq uate p re n ata l c are , a s d efin ed b y K ote lc h uck , e t a l.
(K ote lc h uck e t a l, 1 994 ). T his s ig nif ic an t d if f e re n ce p ers is te d i n t h e m ultiv aria te a n aly sis w hile
c o ntr o llin g f o r E G A a t i n itia l v is it, b ody m ass i n dex ( B M I), p re g nan cy w eig ht c h an ge, g esta tio nal a g e
O AT i n itia te d , y ear o f b ir th , m ate rn al a g e a n d s m okin g d urin g p re g nan cy. B ody M ass I n dex a n d
pre g nan cy w eig ht c h an ge w ere s im ila r b etw een t h e t w o g ro ups. D eliv ery m eth ods w ere a ls o s im ila r
b etw een t h e t w o g ro ups, w ith a p pro xim ate ly 3 0% o f w om en d eliv erin g v ia c esa re an s e ctio n.
Ta ble 2
P re n ata l C hara cte ris tic s
M eth ad on e
(N =248)
B upre n orp hin e
(N =361) P
N m ( s d ) o r n ( % ) N m ( s d ) o r n ( % )
EG A a t i n itia l v is it ( w ks) 2 44 12.2 ( 6 .4 ) 357 11 .7 ( 6 .3 ) .2 96
In itia l v is it i n 1 t r im este r 2 44 160 ( 6 6% ) 357 254 ( 7 1% ) .3 44
A deq uate p re n ata l c are ( K ote lc h uck ) 236 212 ( 9 0% ) 349 329 ( 9 4% ) .0 46
B ody M ass I n dex a t i n itia l v is it 1 90 25.1 ( 5 .3 ) 342 24.6 ( 5 .6 ) .3 31
P re g nan cy w eig ht c h an ge ( lb s) 1 89 26.3 ( 1 7.4 ) 339 26.4 ( 1 6.9 ) .9 13
C esa re an -s e ctio n d eliv ery 2 48 80 ( 3 2% ) 361 104 ( 2 9% ) .3 62
M ate rn al O AT p rio r t o c o ncep tio n 225 95 ( 3 9.7 % ) 342 196 ( 6 0.3 % ) <0.0 001
G esta tio nal a g e O AT i n itia te d ( w eek s) 1 24 18.9 ± 19.1 1 37 15.9 ± 8.1 0 .0 06
M ed ic atio n d ose a t d eliv ery ( m g) 237 87.4 ( 4 9.9 ) 354 15.4 ( 6 .4 ) N /A
E G A, E stim ate d g esta tio nal a g e; m , M ean ; s d , S ta n d ard D ev ia tio n ; O AT, O pia te a g onis t t h era p y ;
in clu des o nly p atie n ts i n itia te d d urin g p re g nan cy
W om en t r e ate d w ith b upre n orp hin e w ere m ore l ik ely t o b e o n a n O AT a t t im e o f c o ncep tio n. F or t h ose
w om en n ot i n t r e atm en t p rio r t o p re g nan cy, O AT w ith b upre n orp hin e w as i n itia te d a t a n e arlie r
g esta tio nal a g e c o m pare d t o m eth ad one.
N in ete en w om en c h an ged t h eir O AT t y pe d urin g p re g nan cy f ro m b upre n orp hin e t o m eth ad one. E le v en
o f t h ese w om en w ere t r a n sitio ned t o t h e m ore i n te n siv e a n d s tr u ctu re d m eth ad one p ro gra m d ue t o i llic it
u se o f o th er s u bsta n ces ( n = 7) o r n onco m plia n ce w ith a p poin tm en ts o r c o unse lin g ( n = 4). F iv e w om en
re q ueste d t h e c h an ge d ue t o s u boptim al c o ntr o l o f s y m pto m s o r o th er m ed ic atio n r e la te d e ff e cts ( n = 3)
or b ecau se t h ey c o uld n ot b e c erta in t h at b upre n orp hin e w ould b e a v aila b le f o r l o nger t h an t h e
im med ia te p ostp artu m p erio d ( n = 2). T hre e w om en w ere s w itc h ed f o r u nknow n r e aso ns. W e i d en tif ie d
st
*
* 4/26/2018 Methadone and buprenorphine for opioid dependence during pregnancy: A retrospective cohort study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375023/ 7/11
4 w om en t h at w ere t r e ate d w ith b upre n orp hin e e arly i n p re g nan cy b ut n ot i n t r e atm en t a t d eliv ery ( a n d
not i n clu ded i n t h e s tu dy). O f t h ese w om en , o ne w ean ed ( s e lf -d ir e cte d ); o ne w as n ot c o m plia n t w ith
o ff ic e-b ase d t r e atm en t, d eclin ed a lte rn ativ e t r e atm en t, a n d l e ft t h e p ra ctic e; a n d 2 w ere l o st t o f o llo w -
up a fte r b upre n orp hin e i n itia tio n. N o w om en w ere t r a n sitio ned f ro m m eth ad one t o b upre n orp hin e.
N ew born o utc o m es a re s h ow n i n T ab le 3 . M ate rn al t r e atm en t w ith b upre n orp hin e, w hen c o m pare d w ith
m eth ad one, w as a sso cia te d w ith s ig nif ic an tly l o nger g esta tio nal a g e, r e d uced i n cid en ce o f p re te rm
b ir th , l a rg er b ir th w eig ht a n d h ead c ir c u m fe re n ce. D if f e re n ces i n g esta tio nal a g e a n d p re te rm b ir th
r e m ain ed s ig nif ic an t i n t h e m ultiv aria te a n aly sis . S ta n dard iz ed b ir th w eig ht a n d h ead c ir c u m fe re n ce ( z -
sc o re s) w ere s im ila r b etw een t h e t w o g ro ups i n t h e u niv aria te a n aly sis .
T a ble 3
N ew born O utc o m es
M eth ad on e
(N =248)
B upre n orp hin e
(N =361) P
In fa n t C hara cte ris tic s N m ( s d ) o r n ( % ) N m ( s d ) o r n ( % )
Male 2 48 111 ( 4 5% ) 361 177 ( 4 9% ) .2 99
E G A a t d eliv ery ( w ks) 2 48 38.2 ( 2 .5 ) 361 39.2 ( 2 .2 ) < .0 01
P re te rm ( E G A<37 w ks) 2 48 43 ( 1 7% ) 361 36 ( 1 0% ) <.0 01
B ir th w eig ht ( g ra m s) 2 48 2899.7 ( 5 83.1 ) 361 3143.3 ( 5 78.9 ) < .0 01
S ta n dard iz ed ( z -s c o re ) 2 48 − 0.5 9 ( .9 3) 361 − 0.4 6 ( .9 8) .0 89
< 5 p erc en tile 2 48 32 ( 1 3% ) 361 40 ( 1 1 % ) .4 94
H ead c ir c u m fe re n ce ( c m ) 209 33.0 ( 2 .0 ) 279 33.6 ( 2 .1 ) < .0 01
S ta n dard iz ed ( z -s c o re ) 2 09 − 0.5 0 ( .8 0) 279 − 0.4 6 ( .9 8) .6 69
In fa n ts t r e ate d f o r N AS 245 106 ( 4 2% ) 358 82 ( 2 3% ) <0.0 01
D ura tio n o f t r e atm en t f o r N AS ( d ay s) 1 06 133± 83 79 83± 60 < 0.0 01
L en gth o f s ta y, E G A ≥ 3 7 w ks, ( d ay s) 2 05 5.6 ( 2 .8 ) 325 4.2 ( 1 2.6 ) .1 07
B re ast m ilk a t d is c h arg e 247 156 ( 6 3% ) 358 267 ( 7 5% ) .0 03
D is c h arg ed i n c are o f m oth er/f a m ily 2 48 237 ( 9 6% ) 360 351 ( 9 8% ) .1 89
E G A, E stim ate d g esta tio nal a g e; m , M ean ; s d , S ta n d ard D ev ia tio n ; N AS, N eo nata l a b stin en ce s y ndro m e
B upre n orp hin e e x pose d n ew born s r e q uir e d m ed ic atio n f o r N AS l e ss f re q uen tly a n d f o r a s h orte r
d ura tio n c o m pare d t o m eth ad one-e x pose d n ew born s. T hese d if f e re n ces w ere s ig nif ic an t i n b oth t h e
univ aria te a n d m ultiv aria te s e ttin g c o ntr o llin g f o r E G A a t i n itia l p re n ata l v is it, a d eq uacy o f p re n ata l
c are , n ullip arity , m ate rn al B M I, m ate rn al p re g nan cy w eig ht c h an ge, g esta tio nal a g e m ate rn al O AT
in itia te d , y ear o f b ir th , m ate rn al a g e a n d s m okin g d urin g p re g nan cy. B upre n orp hin e e x pose d i n fa n ts
h ad h ig her r a te s o f b re astf e ed in g a t d is c h arg e. O ver 9 5% o f n ew born s i n b oth g ro ups w ere d is c h arg ed
to t h e c are o f t h e m oth er a n d/o r f a m ily m em bers . T w o i n fa n ts h ad c o ngen ita l m alf o rm atio ns a t b ir th :
one i n fa n t b orn t o a m oth er t h at c o nceiv ed w hile b ein g t r e ate d w ith m eth ad one h ad a n a b se n t h an d;
th 4/26/2018 Methadone and buprenorphine for opioid dependence during pregnancy: A retrospective cohort study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375023/ 8/11
G o to :
an oth er i n fa n t b orn t o a m oth er t h at c o nceiv ed w hile b ein g t r e ate d w ith b upre n orp hin e h ad a n i s o la te d
c le ft p ala te .
A lth ough n ot i n clu ded i n t h e s tu dy i t i s i n te re stin g t o n ote , t h at 7 f e tu se s b orn t o s ix m oth ers w ere
s tillb orn . O f t h e 5 s tillb ir th s b orn t o 4 m oth ers ( o ne t w in ) t r e ate d w ith m eth ad one, 1 m oth er h ad s e v ere
p neu m onia w ith s e p tic s h ock a t 2 6 w eek s, 1 m oth er p re se n te d f o r a n u ltr a so und a n d w as n ote d t o h av e
a f e ta l d em is e a t 3 8 w eek s w ith i n tr a u te rin e g ro w th r e str ic tio n, 1 m oth er e x perie n ced u te rin e r u ptu re a t
3 2 w eek s f o llo w in g a m oto r v eh ic le a ccid en t r e su ltin g i n t h e b ir th o f s tillb orn t w in s. O ne m oth er
p re se n te d i n l a b or w ith a f e ta l d em is e a t 2 6 w eek s ( s h e h ad b een e v alu ate d a t a n oth er i n stitu tio n f o r a
m oto r v eh ic le a ccid en t 2 4 h ours p rio r t o p re se n ta tio n). O f t h e 2 s tillb ir th s b orn t o b upre n orp hin e t r e ate d
m oth ers , 1 m oth er h ad a c o m ple te a b ru ptio n a t 3 9 w eek s a n d t h e o th er h ad p re te rm p re m atu re r u ptu re
o f m em bra n es a t 2 1 w eek s f o llo w ed b y i n ductio n o f l a b or.
D IS C USSIO N
Wom en t r e ate d w ith b upre n orp hin e d urin g p re g nan cy w ere m ore l ik ely t o 1 ) i n itia te O AT t r e atm en t
prio r t o p re g nan cy o r b eg in e arlie r i n p re g nan cy, 2 ) d eliv er a t t e rm a n d h av e a l o nger d ura tio n o f
gesta tio n, 3 ) d eliv er l a rg er n ew born s w ith l a rg er h ead c ir c u m fe re n ces, a n d 4 ) h av e n ew born s t h at d id
n ot r e q uir e m en t t r e atm en t f o r N AS, o r r e q uir e d t r e atm en t f o r N AS f o r a s h orte r d ura tio n o f t im e
co m pare d t o n ew born s e x pose d t o m eth ad one in u te ro . O vera ll, t h ese r e su lts s u ggest t r e atm en t w ith
b upre n orp hin e d urin g p re g nan cy i n a c lin ic al c o nte x t ( a s o ppose d t o a s tr u ctu re d r a n dom iz ed t r ia l) ,
p ro vid es o utc o m es t h at a re a t l e ast a s f a v ora b le a s m eth ad one. T he s ig nif ic an ce o f t h is c o hort i s t h e
fin din g t h at o ff ic e b ase d t r e atm en t d urin g p re g nan cy c an p ro vid e c o m para b le p re g nan cy o utc o m es
o uts id e t h e c o nfin es o f a t ig htly c o ntr o lle d c lin ic al t r ia l.
C om paris o ns o f o utc o m es f ro m r a n dom iz ed a n d n onra n dom iz ed t r ia ls o fte n y ie ld s im ila r o utc o m es, b ut
la rg er e ff e cts s iz es a re f re q uen tly o bse rv ed i n t h e n onra n dom iz ed s tu die s ( I o an nid is e t a l 2 001 ).
C onsis te n t w ith t h is p atte rn , t h e p re se n t n onra n dom iz ed s tu dy o bse rv ed s ig nif ic an t d if f e re n ces b etw een
m ed ic atio n c o nditio ns o n a n um ber o f o utc o m es t h at t r e n ded t o w ard s ig nif ic an ce i n t h e r a n dom iz ed
M OTH ER s tu dy i n clu din g s ig nif ic an tly l o nger g esta tio n, l o w er r a te o f p re te rm d eliv ery , a n d l o w er
p ro portio n o f n eo nate s r e q uir in g t r e atm en t f o r N AS a m ong b upre n orp hin e- a s c o m pare t o m eth ad one-
tr e ate d w om en ( J o nes e t a l 2 010 ). O ne t r e n d i n t h e M OTH ER s tu dy t h at w as n ot b orn e o ut i n t h e
pre se n t s tu dy w as a t e n den cy f o r m ore w om en r a n dom iz ed t o b upre n orp hin e t o d ro p o ut o f t h e s tu dy
pre m atu re ly , l a rg ely d ue t o r e p orts o f d is s a tis fa ctio n w ith t h e m ed ic atio n d urin g t h e i n ductio n p erio d. I n
o ur n on-ra n dom iz ed c o hort, f e w w om en s w itc h ed f ro m b upre n orp hin e t o m eth ad one d ue t o
d is sa tis fa ctio n w ith b upre n orp hin e; o f t h o se w om en i n ducte d o nto b upre n orp hin e d urin g p re g nan cy,
o nly 3 /1 37 ( 2 .2 % ) r e q ueste d a c h an ge t o m eth ad one d ue t o d is sa tis fa ctio n w ith b upre n orp hin e. W e d id
n ot h av e a n y p atie n t l e av e m eth ad one t r e a tm en t d urin g p re g nan cy. T hese f in din gs s u ggest t h at w hen
w om en a re c o nsid ere d c an did ate s f o r o ff ic e b ase d t r e atm en t b ase d o n t h e g en era l S A M HSA g uid elin es,
th ere i s a h ig h c h an ce o f s u ccessfu l i n ductio n a n d t r e atm en t w ith b upre n orp hin e d urin g p re g nan cy. O ur
obse rv atio ns a re q uite r e assu rin g f o r t h o se t h at w an t t o c o nsid er a s te p ped a p pro ach t o t h e t r e atm en t o f
opio id d ep en den ce d urin g p re g nan cy : i d en tif y p atie n ts t h at m ay b e c an did ate s f o r o ff ic e b ase d
tr e atm en t a n d s w itc h o nly i f n eed ed f o r i m pro ved s y m pto m c o ntr o l o r m ore s tr u ctu re d p ro gra m ( K ak ko
et a l, 2 007 ).
O ur f in din gs a re l im ite d b y t h e l a ck o f r a n dom iz atio n a n d r e tr o sp ectiv e n atu re o f t h e d ata c o lle ctio n. I n
th e p ra ctic e o f t r e atm en t, h ow ev er, m ulti p le i s su es a re c o nsid ere d a n d m ultip le o utc o m es a re o f
im porta n ce r e g ard in g p atie n t o utc o m es f ro m a c h ose n t h era p y. I n t h is r e g ard , a c o hort s tu dy t h at a llo w s
fo r p atie n t t r e atm en t s e le ctio n, a sse ssm en t o f a w id e r a n ge o f o utc o m es ( d if f ic u lt i n t ig htly c o ntr o lle d
se ttin gs), a n d m ed ic atio n e ff e ctiv en ess a re q uite u se fu l. W e r e co gniz e t h e l im ita tio ns o f a sse ssin g
cau sa lity i n t h is s tu dy, w hic h i s o ptim ally a d dre sse d b y a r a n dom iz ed t r ia l d esig n ( I o an nid is e t a l,
2 001 ). 4/26/2018 Methadone and buprenorphine for opioid dependence during pregnancy: A retrospective cohort study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375023/ 9/11
G o to :
G o to :
G o to :
G o to :
O ur d ata b ase m ay h av e m is se d w om en t h at i n itia te d t r e atm en t b ut w ere l o st t o f o llo w -u p p rio r t o e n tr y
in to t h e d ata b ase . W e i d en tif ie d 3 w om en i n w hom b upre n orp hin e w as i n itia te d b ut w ere l o st t o f o llo w -
up. N oneth ele ss, o ur f in din gs a re r e fle ctiv e o f t h e a p pro ach m an y c o m munitie s m ay h av e i n t h e
tr e atm en t o f o pio id d ep en den t w om en d urin g p re g nan cy. O vera ll, o ur d ata d em on str a te d a h ig h d eg re e
o f c o m plia n ce w ith p re n ata l c are a n d c o ntin uatio n o f t r e atm en t f o r w om en i n itia te d o r m ain ta in ed o n
bupre n orp hin e d urin g p re g nan cy. I t i s o f n ote t h at a l a rg e m ajo rity o f o ur n eo nate s w ere d is c h arg ed i n to
t h e c are o f a f a m ily m em ber a t b ir th . T his i s p ossib le i n p art d ue t o c lo se f o llo w -u p o f a ll f a m ilie s f o r a t
le ast a y ear a fte r b ir th i n a s ta te s u pporte d p ro gra m .
The p re se n t s tu dy i s t h e l a rg est c o hort c o m parin g p re g nan cy o utc o m es i n w om en t r e ate d w ith
m eth ad one v s. b upre n orp hin e i n t h e U nite d S ta te s. O ur f in din gs a re r e assu rin g f o r o pio id t r e atm en t i n
g en era l, a s b oth g ro ups d em onstr a te d g ood c o m plia n ce w ith p re n ata l c are a n d o ver 9 5% o f i n fa n ts w ere
d is c h arg ed t o t h e c are o f t h e m oth er o r f a m ily . B ecau se o f t h e c o hort s iz e a n d r e assu rin g o utc o m es,
th ese d ata a d d s ig nif ic an tly t o t h e l ite ra tu re e x am in in g t h e e ff ic acy a n d c lin ic al e ff e ctiv en ess o f
bupre n orp hin e f o r t h e t r e atm en t o f o pio id d ep en den ce d urin g p re g nan cy a n d s tr o ngly s u pport i ts u se
b ase d o n s ta n dard c lin ic al c rite ria f o r o ff ic e b ase d t r e atm en t o f o pio id d ep en den ce.
C onclu sio ns
Pre g nan cy o utc o m es o f o ff ic e b ase d t r e atm en t f o r o pio id d ep en den ce d urin g p re g nan cy w ith
b upre n orp hin e a re a t l e ast c o m para b le t o o utc o m es o bse rv ed w ith d aily d osin g w ith m eth ad one.
N eo nata l a b stin en ce i s r e d uced i n t h e p atie n ts t r e ate d w ith b upre n orp hin e i n t h is c o hort.
A ckn ow le dgem ents
W e t h an k M au re en M atth ew s R N a n d J e rily n M eta y er R N , w ho k in dly p ro vid ed t h e d ata n ecessa ry f o r
our a n aly sis b y m ain ta in in g t h e Q uality A ssu ra n ce d ata b ase u se d i n t h is s tu dy.
F undin g S ou rc e: P re p ara tio n o f t h is m an usc rip t w as s u pp orte d i n p art b y R 34D a0 30534 a n d R 01
D A031928 f ro m t h e N atio nal I n stitu te o n D ru g A buse . S upport f o r m ain te n an ce o f t h e Q uality
A ssu ra n ce d ata w as s u pporte d b y t h e V erm ont C hild H ealth I m pro vem en t P ro gra m . N eith er N IH n or
V CH IP h ad a n y f u rth er r o le i n s tu dy d esig n; i n t h e c o lle ctio n, a n aly sis a n d i n te rp re ta tio n o f d ata ; i n t h e
w ritin g o f t h e r e p ort; o r i n t h e d ecis io n t o s u bm it t h e p ap er f o r p ublic atio n.
C ontr ib uto r In fo rm atio n
M arjo rie C . M ey er, D ep artm en t o f O bste tr ic s, G yneco lo gy & R ep ro ductiv e S cie n ces, U niv ers ity o f
V erm ont, B urlin gto n, V T, U nite d S ta te s.
A nne M . J o hnsto n, D ep artm en t o f P ed ia tr ic s, U niv ers ity o f V erm ont, B urlin gto n, V T, U nite d S ta te s.
A big ail M . C ro ck er, D ep artm en t o f M ath em atic s a n d S ta tis tic s, U niv ers ity o f V erm ont, B urlin gto n, V T,
U nite d S ta te s.
S ara h H . H eil, D ep artm en ts o f P sy ch ia tr y a n d P sy ch olo g y, U niv ers ity o f V erm ont, B urlin gto n, V T,
U nite d S ta te s.
R EFE R EN CES
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bupre n orp hin e, m eth ad one a n d h ero in o n t h e c o urs e o f p re g nan cy, b ir th w eig ht o f n ew born s, 4/26/2018 Methadone and buprenorphine for opioid dependence during pregnancy: A retrospective cohort study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375023/ 10/11
e arly p ostp artu m a d ap ta tio n a n d c o urs e o f t h e n eo nata l a b stin en ce s y ndro m e ( N AS) i n w om en
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2 2 . S A M HSA : S ubsta n ce A buse a n d M en ta l H ealth S erv ic es A dm in is tr a tio n. C lin ic al G uid elin es f o r
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