ORIGINAL PAPER

Perinatal outcome of illicit substance usein pregnancy—comparative and contemporarysocio-clinical profile in the UK

Nitin Goel & Dana Beasley & Veena Rajkumar &

Sujoy Banerjee

Received: 7 June 2010 /Accepted: 17 August 2010 /Published online: 9 September 2010# Springer-Verlag 2010

Abstract The aim of the study was to determine thecontemporary socio-clinical profile and perinatal outcomeof illicit substance use in pregnancy in a large UK city andcompare with published literature. Cases were identifiedretrospectively from the ‘cause for concern’ referrals over5 years (2003–2007). Data was collected on mother–infantpair from medical notes and laboratory records. Chi-squareand Mann–Whitney U tests were used where appropriatefor statistical analysis. One hundred sixty-eight womenwere identified as using illicit substance in pregnancy.Smoking (97.4%), unemployment (85.4%) and single status(42.3%) were frequent. Besides controlled use of metha-done, heroin, cannabis and benzodiazepines were the mostcommonly used drugs. Hepatitis C prevalence was high(29.9%) despite low antenatal screening rates (57.7%).Neonatal morbidity was related to prematurity (22.9%),small for dates (28.6%) and neonatal abstinence syndrome(NAS; 58.9%). By day 5 of life, 95.1% of the babiesdeveloping NAS and 96.1% of those requiring pharmaco-

logical treatment were symptomatic. Of the infants devel-oping NAS, 31.7% required pharmacological treatment. Atotal of 82.5% babies went home with their mother, and21.2% were placed on the Child Protection Register. Only14.3% were breast feeding at discharge. Illicit substance usein pregnancy continues to be associated with significantmaternal and neonatal morbidity, and the socio-clinicalprofile in this decade appears unchanged in the UK.Hepatitis C prevalence is high, and detection should beimproved through targeted antenatal screening. Wherefacility in the community is unavailable, 5 days of hospitalstay is sufficient to safely identify babies at risk ofdeveloping NAS. Most babies were discharged home withtheir mother.

Keywords Illicit substance use . Substance misuse .

Socio-clinical profile . Perinatal outcome .

Neonatal abstinence syndrome

Introduction

Illicit substance use continues to be a major public healthproblem in the UK [4]. Around 10% of adults aged 16–59 years, 22% aged 16–24 years and 8% aged 24–29 yearsreported using any illicit drugs in 2008/2009 in Englandand Wales [8]. Substance-using women are mostly ofchildbearing age, and 18% of women between 16 and24 years of age report drug use [8].

Substance use in pregnancy poses significant health risksfor the mother, foetus and the newborn child and requiresspecialist care. Maternal risks are secondary to socioeco-nomic and lifestyle issues, infection-related morbidities,hazards related to the specific substance use and itsprocurement. Women constitute a quarter of the treatment

N. Goel :D. Beasley :V. Rajkumar : S. BanerjeeDepartment of Neonatal Medicine, Division of Women and ChildHealth, ABM University Health Board, Singleton Hospital,Sketty Lane,Swansea SA2 8QA, UK

N. Goele-mail: drnitingoel@yahoo.co.in

D. Beasleye-mail: danabeasley@doctors.org.uk

V. Rajkumare-mail: veenadoc@doctors.net.uk

S. Banerjee (*)15 Alder Way, Westcross,Swansea SA3 5PD, UKe-mail: sujoybanerjee@doctors.org.uk

Eur J Pediatr (2011) 170:199–205DOI 10.1007/s00431-010-1284-6

population of substance use services, and over 90% are ofchildbearing age [3]. These women are known to be poorlycompliant and disengaged with healthcare resources, andthe extent and ease with which such services are availableare extremely variable across the country. The exact scopeof the problem is unknown, as it relies much on voluntarydisclosure [15].

The foetal risks are related to the effect of the substanceand associated maternal lifestyle on the developing organsand placental function. Newborns are at risk of being bornearly and small, acquire perinatal infection and developneonatal abstinence syndrome (NAS). The practice ofprolonged hospitalisation, for identification and treatmentof NAS, as well as to resolve any outstanding childprotection issue, is variable in the UK. It is disruptive tothe family with likely effects on bonding and establishmentof breast feeding. A recent survey of UK neonatal units(NNU) showed that 29% of them discharged babies onmedications to avoid prolonged hospitalisation [17].

Published data in the UK on perinatal outcomes of illicitsubstance use in pregnancy is sparse and mostly from verylarge cosmopolitan cities. Swansea is the second largest cityin Wales and has a single large maternity unit that manageshigh-risk pregnancies. The catchment is a mixture of urban,semi-urban and rural population that has a higher unem-ployment and lower socioeconomic status than the Welshaverage [23]. The ‘Swansea Drugs Project’ is one of theoldest substance misuse agencies in Wales that worksclosely with the community drug and alcohol team.

The aim of this 5-year retrospective observational studywas to determine the contemporary socio-clinical profileand perinatal outcome of illicit substance use in pregnancyin a large UK city. We focussed on specific maternal andneonatal outcomes including utilisation of hospital inpatientservices and compared our findings with published data inthe UK and from the rest of the world.

Methods

This retrospective observational study was undertakenbetween January 2003 and December 2007. The studywas part of service evaluation and audit of standards of carein pregnancies with illicit substance use against local andnational guidelines [4]. The study was registered with thetrust audit register, and the local research ethics committeehas confirmed that there are no ethical issues related topublication of the results.

Pregnant women with history of illicit substance usewere identified from the ‘Cause for Concern’ referralrecords at our hospital. Such referrals were usually madeduring the pregnancy following maternal disclosure to themidwife at booking or subsequently to other carers or

agencies. Maternal disclosure was relied on to ascertaindrug use rather than urinary drug screens, as the latter onlyprovided a cross-sectional snapshot and was unlikely todetect all illicit drugs. Additionally, poor compliance inagreeing to the test was likely to underestimate the trueprevalence. Women who had miscarriage or stillbirths orused prescribed medicines for pre-existing medical con-ditions were excluded. Women with previous history ofdrug use who abstained during this pregnancy were alsoexcluded. For each mother–infant pair identified, a prede-fined dataset was completed using information from themedical case notes, laboratory records and other hospitaldatabases.

Maternal demographic details, social history, profile ofillicit substance use and information on antenatal careincluding results of infection screen were collected. Poly-drug use was defined as use of more than one illicit drugexcluding alcohol and tobacco.

Neonatal data included gestation, birth weight, mode ofdelivery and details of postnatal observations for detectionof NAS. The hospital guideline for the management ofNAS was extensively revised and implemented in 2007.Prior to this (2003–2006), infants born to substance-usingmothers were required a mandatory hospital stay of14 days to monitor symptoms of NAS. This was reducedto 7 days in 2007. Symptoms of NAS were recordedusing the modified Lipsitz tool from 2003 to 2006 andmodified Finnegan score in 2007. These two scoringsystems, although relying heavily on observational meas-urements, are the most commonly used in the UK and therest of the world [15, 17]. A persistent score of greater than4 points on the Lipsitz scale and three scores of 8 points ina 24-h period on the Finnegan scale were generallyregarded as threshold for pharmacological intervention [5,12]. For the purpose of this study, infants scoring 2 pointson the Lipsitz scale and 4 points on the Finnegan scale wereregarded as ‘withdrawing’.

Reasons for admission to the NNU were identified. Allbabies requiring pharmacological treatment were admittedto the NNU. Co-morbidities including prematurity (<37completed weeks of gestation), small for date (less thantenth centile), hypoglycaemia (<2.6 mmol/l on laboratorymeasurement or equivalent on point of care equipment),method of feeding and need for sepsis evaluation wererecorded.

Babies of seropositive mothers (HBsAg±HbeAg posi-tive) and those at high risk of acquiring hepatitis B virus(HBV) infection, i.e. history of intravenous drug use,received hepatitis B vaccine±immunoglobulin as appro-priate. Follow-up data on HBV immunisation and sero-conversion was obtained. Data was also collected ondischarge destinations and enrolment on the ChildProtection Register.

200 Eur J Pediatr (2011) 170:199–205

Anonymised data was analysed on Microsoft Excel2003. In some categories, data was incomplete due to lackof documentation or unavailability of clinical notes. Whenreporting results, we have indicated the denominator ineach category. Cohort characteristics were expressed asproportion, median and range as appropriate. Whereappropriate, the non-parametric Mann–Whitney U test orChi-square analysis of 2×2 contingency tables was used todetermine the significance of outcome differences betweenindependent groups of continuous or categorical variables,respectively. p<0.05 was considered to be statisticallysignificant.

Results

Of the 17,856 pregnancies in this period, 168 (0.9%) wereidentified with history of illicit substance use in the currentpregnancy.

Maternal outcome

The demographic characteristics of the women are shownin Table 1.

Of the 168 women who disclosed to definite use ofillicit drugs in pregnancy, we had detailed informationon the type of drugs used for 132 women. In theremaining 36 women, despite indirect evidence of druguse in many, we could not be entirely sure of the rangeor type of illicit drugs used due to unavailability ofclinical notes. We have reported them as ‘unspecified’drug use. Besides controlled use of methadone, heroin,cannabis and benzodiazepines were the most frequentlyused street drugs (Fig. 1). Polydrug use as defined wasnoted in 81/132 (61.3%) women. Seventy-two women(54.5%) were on the methadone programme, but of these,54 (75%) used additional drugs. Where notes containedexplicit data, tobacco smoking was seen in 116/119(97.4%) and alcohol abuse in 42/87 (48.3%). If alcoholand tobacco use were included in the definition of

polydrug use, 128/132 (97%) would have been classifiedas polydrug users. Opiates were used by 74 of the 81polydrug users (91.4%) and 30 of 51 monodrug users(58.8%). Thirty-seven women used benzodiazepines, all aspart of polydrug use.

Fifty-three of 64 (82.8%) known partners were also drugusers. Exposure to domestic violence was seen in 17 out of81 (21%) women where this information was specificallyrecorded. A previous child was in care in 29 cases. Of the94 women receiving regular antenatal care, 22 (23.4%)were late bookers (>20 weeks).

Table 2 shows the results of the antenatal serologyscreening. There was no new HBV infection in the last3 years or any positive case of human immunodeficiencyvirus (HIV) in the entire study period.

Neonatal outcome

Thirty-two of 140 (22.9%) babies were born premature, ofwhich 30 (93.7%) were born at a gestation greater than32 weeks. The mean birth weight was 2.76 kg (95% CI,2.65, 2.87), but 40 (28.6%) were small for dates (SFD).There was no neonatal death. Table 3 shows the pattern ofcommon neonatal morbidities.

In 26/136 babies (19.1%), septic screen was performedto rule out infection, and antibiotics were given, pendingblood culture reports. There were no positive cultures.

Eighty-two of 139 babies (58.9%), where records ofwithdrawal scores were available, developed withdrawalsymptoms. A higher proportion of babies withdrew in thepolydrug user group (56 of 81) as compared to monodrugusers (26 of 51), and this difference was statisticallysignificant (p=0.03). Methadone was part of the mother'ssubstance use in 54 out of the 82 babies (65%) with NAS.Of the 72 babies in the maternal methadone use group, 23required pharmacological treatment as compared to 1 out of28 in the non-methadone opiate use (p=0.006). Of the 37babies with maternal benzodiazepine use, 24 (64.9%)developed NAS, and seven (18.9%) required pharmacolog-ical treatment.

By day 5, 95.1% (78/82) babies who developed NASwere symptomatic, and 81.7% (67/82) had reached theirpeak symptoms. Pharmacologic treatment was required in26/82 (31.7%) babies with NAS. All but one baby(96.1%) requiring pharmacological treatment developedNAS by day 5 of life. There was no significantdifference between groups of polydrug and monodrugusers regarding incidence of pharmacological interven-tion for NAS (20 vs. 6; p=0.11). All except two babieswere treated with morphine sulphate. The median durationof treatment was 13 days, and the median maximum doseof morphine was 240 mcg/kg/day. Chloral hydrate wasused in conjunction with morphine in nine cases. The

Table 1 Maternal demographics

Characteristic Results

Maternal age in years: median (range) 25 (16–39)

Smoking 116/119 (97.4)a

Heavy smoker (>10 cigarettes a day) 53/102 (51.9)a

Unemployed 94/110 (85.4)a

Unmarried 101/111 (91)a

Without a current partner 47/111 (42.3)a

a n/records available (percent)

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remaining two babies were treated with phenobarbitoneand chlorpromazine, respectively.

Fifty-nine of 168 babies (35.1%) were admitted to NNU.Pharmacological treatment for NAS was the most frequentreason for admission to NNU (26/59; 44%). Other reasonsfor admission were prematurity, low birth weight, socialissues and closer monitoring of NAS.

The median hospital stay of infants for the entire studyperiod was 9 days (range, 1–135). The median hospital staywas reduced from 12 days in 2003–2006 to 7 days in 2007,despite a rise in the number of at-risk infants (Figs. 2 and 3).The reduction was not accompanied by a concomitant rise inreadmission rates (p<0.001).

Seventy-one of the 130 babies born to HBV seronegativewomen (HBsAg negative) were offered hepatitis B vacci-nation due to associated risk factors. Only 25 (35.2%)completed the full course of four doses. In contrast, five ofthe seven babies (71.4%) born to HBsAg-positive motherscompleted the full vaccination schedule and remainednegative for HBV infection markers. Two of the sevenHBsAg-positive mothers were also HbeAg positive, andtheir infants received hepatitis B immunoglobulin inaddition to hepatitis B vaccine and completed the fullimmunisation schedule. Twenty-nine babies were born tomothers with positive serology for hepatitis C virus (HCV)infection. Full follow-up data was available in 23 babies,none of whom developed HCV infection.

Discharge outcomes were known for 137 babies, of which113 (82.5%) were discharged home with their mother.Twenty-nine of 137 (21.2%) newborns were placed on theChild Protection Register, while 24/137 (17.5%) were placedin foster care. Of the 24 placed in foster care, 20 had pre-birthsocial services involvement, and the reasons for placementwere a combination of domestic violence, unstable drug use inthe family, concerns regarding parenting capabilities andhistory of previous children in care. Only 19/133 (14.3%)were breastfeeding at discharge.

Discussion

The prevalence of illicit substance use in pregnant womenwas 0.9% (168/17,856) in our study. Recent data from theNorthern Region in the UK and Dumfries in Scotland 2002suggested an incidence of 0.75% and 0.11%, respectively[13, 18]. In a Croatian study (1997–2007), Vucinovic et al.reported a prevalence of 0.2% [21]. Much higher preva-lence has been reported from the US and Australia [11, 15].

The demographic profile of women in our studyconfirms a continuing pattern of very unstable andvulnerable social background that matched closely withstudies from different regions of the UK in this decade(Table 4) [5, 7, 18]. Unemployment and single status werehigh, and majority of known partners were drug users.

Number screened, n/N Percent screened Positive

Hepatitis B 137/168 81.5 7 (5.1%)

Hepatitis C 97/168 57.7 29 (29.9%)

HIV 125/147a 85 All negative

Syphilis 108/168 64.3 All negative

Chlamydia 65/168 38.7 11 (16.9%)

Table 2 Antenatal infectionscreening

N total pregnancies identifieda Denominator=records available

Fig. 1 Pattern of substance use

202 Eur J Pediatr (2011) 170:199–205

Tobacco smoking was a universal cohabit, and 50% ofwomen smoked heavily.

Besides controlled use of methadone, heroin andcannabis were the most frequent drugs used in pregnancy,similar to other reports from the UK [7, 13, 18]. In contrast,in the UK general population, cannabis and cocaine are themost commonly used drugs [8]. Heroin use is known to behigh in a population like ours with low socioeconomicstatus. Cannabis use may have been underreported bywomen in view of its minimal effect on neonatal absti-nence. Polydrug use was common, despite an activemethadone programme. This trend is similar to that notedin other studies [1, 2, 9, 24].

The lifestyle associated with drug use increasesvulnerability to infection. Our study cohort had no HIVinfection, a low prevalence of HBV but a relatively highHCV infection. The prevalence of HBV, HCV and HIVinfection among intravenous drug users in the UK were21%, 50% and 1%, respectively, with geographicvariations [8]. Analysis of paired HCV and HIVprevalence data has shown that HCV prevalence of upto 30% is associated with zero or very low prevalence ofHIV [6]. The prevalence of HCV infection had risen fromour own historic data (5% in 1997–2002, unpublished) butmatched closely with reports from other parts of the UK[7, 18]. Higher prevalence has been reported in Europeand by studies examining specifically intravenous drug

users [6, 10, 13]. However, of major concern is the lowHCV screening rate coupled with its high prevalence.Screening for HCV is not part of the routine antenatalscreening in the UK. Treatment for HCV infection iseffective and widely available. There is a need to improveawareness, counselling and screening rates of HCVinfection in this population.

Prematurity (21.9%) was common in our cohort, muchhigher than the reported 6% in the general population [16].Although more than a quarter of the infants were SFD, themean birth weight of 2.76 kg was similar to other reports[7, 9, 10, 21]. The higher proportion of non-instrumentaldeliveries (82% vs. 60–70% in Welsh population) could beexplained by the small size of the babies secondary toprematurity and SFD [22]. Despite a lack of culture-provensepsis, many sepsis evaluations were undertaken due tooverlap of symptoms of NAS and early onset sepsis.

The incidence of NAS (58.9%) was similar to thatreported elsewhere [5, 12, 21]. The higher incidence ofNAS with maternal polydrug use could be explained bygreater opiate use in this group as compared to those usinga single drug (91.35% vs. 58.8%). Methadone use,implicated in 65% of our cohort with NAS, has reportedassociation with prolonged and severe NAS [5, 9, 15, 21].

Differences in admission policy, infrastructure for treat-ment of NAS (postnatal ward/community) and the efficien-cy with which safeguarding issues are managed influenceboth NNU admission rate and duration of hospital stay.Pharmacological treatment of NAS on the postnatal ward ascompared to NNU has been shown to reduce total durationof hospital stay [19]. A study of practices of NASmanagement in the UK found inconsistent policies inhospitals for its detection and treatment [20]. Our organi-sation did not have the facility to institute pharmacologicaltreatment on the postnatal ward or in the community.However, mothers had full access to their children at alltimes and took part in routine postnatal care. Despite afalling trend, greater than a third of the at-risk newbornsrequired admission to NNU. The fall in NNU admissioncould be attributed to better recognition of NAS severity

29 30

36

25

38

1210

11.514

7

0

10

20

30

40

2003 2004 2005 2006 2007

Nu

mb

er o

f in

fan

ts

At risk infantsHospital stay (days)

Fig. 3 Duration of hospital stay

Fig. 2 Admissions to the neonatal unit

Table 3 Neonatal morbidity

Characteristic Resulta

Prematurity 32/140 (22.9)

Small for gestation age (<tenth centile) 40/140 (28.6)

Hypoglycaemia (<2.6 mmol/l) 27/136 (19.8)

Sepsis screen 26/136 (19.1)

Instrumental/caesarean delivery 23/133 (17.3)

Resuscitation at birth 13/136 (9.6)

a n/records available (percent)

Eur J Pediatr (2011) 170:199–205 203

and institution of non-pharmacological treatment on thepostnatal ward. The duration of hospital stay in our cohortwas shorter than some reports, but similar to that reportedfrom Hull [2, 7, 15]. The median hospital stay reducedfollowing introduction of new guidelines without a con-comitant increase in readmission rates.

The use of morphine sulphate in our study for treatmentof NAS was similar to other reports from UK andelsewhere [15, 17, 20]. The median duration of pharmaco-logical treatment was lower than that previously reported[9]. The reasons are unclear but may be secondary to betterantenatal control and consistent treatment regimens.

Our finding that 95.1% of the babies developing NASand, more crucially, 96.1% requiring pharmacologicaltreatment were symptomatic by day 5 of life is highlysignificant. We recommend that health infrastructures thatdo not have facilities for detection and management ofNAS in the community could safely reduce the durationof in-hospital stay to identify infants at risk of NAS to5 days thereby freeing up acute hospital beds andaccompanying resources. Previous reports had alsosuggested that delayed presentation of NAS is uncom-mon even in methadone users [12]. Oei et al. hadsuggested a similar plan of action, but only throughcoordinated outpatient care [14, 15].

We had no vertical transmission of HCV or HBV.Despite appropriate initiation of hepatitis B vaccination,compliance with the full vaccination schedule was poor.The poor compliance is likely due to asymptomatic status,lack of awareness and frequent change of abode in thiscohort. Compliance was worse in infants of HBV seroneg-ative mothers.

Despite active encouragement for breast feeding, only14.3% babies were breastfed at discharge as compared to50% in our general population. Four out of five babies weredischarged home with their mother, similar to reportedtrends in UK and elsewhere [5, 7, 10]. We do not have datato determine if this pattern was sustained in the long term.Majority of foster placements were determined by pre-birthconferences and due to multiple social factors.

Our study has limitations. As a retrospective study, wehad to rely on documentations in the case notes. There weremissing data in some categories, but they constituted only asmall proportion of the results reported. We are thereforeconfident that our data is representative of our population.We did not collect data on miscarriages and stillbirths.Majority of such events occurred even before a disclosureor ‘cause for concern’ was raised and therefore would haveled to serious underestimates of such outcome. We did nothave specific information on intravenous drug use or long-term follow-up data on most outcomes beyond hospitaldischarge. Future studies should address these deficiencies.

Limitations withstanding, our paper highlights importantand contemporary socio-clinical profile of substance use inpregnancy and its effect on maternal and neonatal morbid-ity. These are likely to be important in planning anddelivery of healthcare to this vulnerable group.

Conclusion

Illicit substance use in pregnancy continues to be associatedwith significant maternal and neonatal morbidity and avulnerable social background. The socio-clinical profileover the last decade appears similar in reported studiesacross urban areas in the UK. Hepatitis C prevalence ishigh, and detection through targeted antenatal screeningshould be improved. Where monitoring facilities are notavailable in the community, 5 days of hospital stay issufficient to safely identify babies at risk of developingNAS. Majority of the babies are discharged home with theirmother (Appendix).

Acknowledgements We would like to thank Virginia Hewitt, leadmidwife for vulnerable adults and children, for her suggestions in theformative stage of the study and Cerys Nicholls for her help incollecting maternal data. We would like to thank the audit departmentat Singleton Hospital and Mrs. Lynda Challacombe for their help inobtaining medical notes.

Conflict of interest The authors declare no conflict of interest.

Hull 1997–2003 [7] Dumfries 2001–2005 [18] Swansea 2003–2007

Maternal age 23–25 years* 25 years* Median 25 years

Smoking – 100% 98.3%

Unmarried 83% – 91%, 42.3% single

Unemployed 87% – 85.4%

Drug use Heroin, methadone Heroin, methadone, cannabis Methadone, heroin, cannabis

Hepatitis C 40% of screened 35% of screened 29.9% of screened

Hepatitis B 4% of screened Nil 5.1% of screened

Discharged home 80.8% 94% 82.5%

Breast feeding 19% – 14.3%

Table 4 Comparative data onreported maternal and neonataloutcomes of substance usein pregnancy in the UK(1997–2007)

*Mean value

204 Eur J Pediatr (2011) 170:199–205

Appendix

References

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8. Hoare J (2009) Drug misuse declared: findings from the 2008/09British Crime Survey—England and Wales. Home Office Statis-tical Bulletin, London. http://rds.homeoffice.gov.uk/rds/pdfs09/hosb1209.pdf. Accessed 3 Jun 2010

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Table 5 Summary points

What is already known on this topic?

• Illicit substance use in pregnancy is associated with significantmaternal and neonatal morbidity

• Management of mother and newborn child varies widely acrossthe UK and Europe

• Hepatitis C infection screen is not part of the routine antenatalscreening programme in the UK and in many European countries

What this study adds?

• The socio-clinical profile of illicit substance use in pregnancyover the last decade appears similar and unchanged in reportedstudies across urban areas in the UK

• Hepatitis C prevalence is high despite low screening rates, anddetection should be improved through targeted antenatalscreening

• Where monitoring facilities are not available in the community,5 days of hospital stay is sufficient to safely identify babies at risk ofdeveloping NAS. This finding has important implication forresource allocation and safe planning of health care delivery in thisvulnerable population

• Majority of the babies are discharged home with their mother inthe UK

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