Abstract
Background
Excessive alcohol use during pregnancy has been associated with adverse maternal and neonatal effects. It is therefore important to develop and evaluate effective interventions during this important time in a woman's life. To our knowledge there have been no systematic reviews of randomised control trials (RCT) in this population.
Objectives
To evaluate the effectiveness of pharmacologic interventions in pregnant women enrolled in alcohol treatment programs for improving birth and neonatal outcomes, maternal abstinence and treatment retention.
Search methods
We searched the Cochrane Drugs and Alcohol Group's Trial register (August 2008) ; MEDLINE (1.1950 to 6.2008) ; EMBASE (1.1974 ‐ 8.2008); CINAHL (1.1982‐6.2008); PsycInfo (1.1806‐6.2008), and reference lists of articles.
Selection criteria
We sought to include randomised or quasi‐randomised studies comparing any pharmacologic intervention versus other pharmacologic treatment alone or in association with psychosocial treatment, placebo, non‐intervention or psychosocial intervention.
Data collection and analysis
Two review authors independently assessed trials for inclusion in the review. Included studies were to be assessed using standardized data extraction and quality assessment forms. No suitable trials were identified.
Main results
The search strategy identified 793 citations. Twenty‐three citations were deemed relevant for full text review; an additional ten articles were retrieved through hand searching references, for a total of thirty‐three articles. Following full text review no articles met the inclusion criteria. Data extraction and assessment of methodological quality were therefore not possible.
Authors' conclusions
The review question remains unanswered as there were no randomised control trials found relevant to the topic. There is a need for high quality research to determine the effectiveness of pharmacologic interventions in pregnant women enrolled in alcohol treatment program.
Plain language summary
Pharmacologic interventions for pregnant women enrolled in alcohol treatment programs
Drinking alcohol during pregnancy is common. Yet no safe level of alcohol consumption is known, with no conclusive evidence on any adverse effects on the unborn child with low levels of alcohol. During pregnancy, more than two units per day or more than four units per drinking session may increase the risk of miscarriage, reduce growth, and impair mental development of the baby. Foetal alcohol syndrome is evident as neurological abnormalities, mental retardation, varying degrees of psychosocial and behavioural problems and characteristic facial dysmorphology that are apparent in adolescents and adults. In some populations alcohol use during pregnancy leads to increased child abuse and neglect or compromised mother‐infant attachment and responsiveness. Mothers who consume alcohol are more likely to have post‐natal depression and are less likely to attend health facilities for education and medical treatment. Specific interventions need to be put in place to assist pregnant and postpartum women who have alcohol problems. Medicines are given to assist with alcohol treatment by lessening the effects during detoxification. These include benzodiazepines, phenothiazines and chlormethiazone, used to reduce anxiety and insomnia. Anti‐depressants may also be given after withdrawal. Disulfiram, naltrexone and acamprosate are used in more severe cases to decrease cravings for alcohol and maintain abstinence. The review authors could not identify any randomised controlled trials (RCTs) evaluating the effectiveness of pharmacologic interventions to improve maternal, birth, and infant outcomes in pregnant women enrolled in alcohol treatment programs. The main reason for study exclusion was study design; we found trials without a control group or focusing only on outcomes for the newborn baby such as birth weight, length or head circumference. Given the stigma attached to alcohol use in pregnancy, recruitment for outcomes trials is likely to remain difficult, which adversely affects generalizability. Clearly the availability of quality evidence would assist with ante‐partum decision making by both the physician and mother.
Background
There are ten countries which have recommendations on alcohol use in pregnancy, all stating that women should avoid alcohol while pregnant. Such recommendations of complete abstinence are contrary to the fact that the consumption of alcohol during pregnancy is common (Doggett 2005). In the United States (US), 11.8% of pregnant women reported recent use of alcohol (NSDUH 2006; NSDUH 2007); whereas 75% of pregnant women in Australia reported some alcohol use in the prior twelve months (ONS 2006) and in the United Kingdom (UK), 61% of mothers continued to drink alcohol while they were pregnant (Taylor 2006). However, these figures are related to 'regular' use of alcohol and therefore are not necessarily at levels where there is evidence of associated harm. For example, the majority (71%) of those in the US who continued to drink consumed less than 1 unit of alcohol per week and only 3% had drunk more than 7 units a week (NSDUH 2006). Some countries including Australia, Spain, and the UK provide broader recommendations on alcohol use during pregnancy and state that if a woman decides to drink she should have no more one to two drinks a week and not binge drink (ICAP 2007).
Even though there is no known safe level of alcohol consumption in pregnancy, there is no conclusive evidence that low level of alcohol consumption has any adverse effects to the unborn child (NICE 2008). However, excessive alcohol use (more than two units per day or more than four units per drinking session) during pregnancy has been associated with increased risk of miscarriage, a reduction in foetal growth and impaired neurodevelopment (AAP 2000; Taylor 2006).
Description of the condition
Along with the detrimental effects to both maternal and foetal health, innumerable costs are incurred to the economy from alcohol use. Alcohol misuse in the UK is estimated to cost in the region of £20 billion (Strategy Unit 2003). In developed countries, alcohol is the third leading cause of ill health after smoking and hypertension. Current estimates are that for every pound spent on effective substance use treatment, five pounds is saved in health and social care costs (Raistrick 2006).
Alcohol use during pregnancy is associated with a wide range of adverse effects. Alcohol is associated with a continuum of birth damage (Barrison 1985) including a combination of developmental delay, growth retardation, neurological abnormalities and characteristic facial dysmorphology referred to as the Foetal Alcohol Syndrome (FAS). Although FAS is the most commonly recognised cause of mental retardation, adolescents and adults with FAS have varying degrees of psychosocial and behavioural problems (Weintraub 1998). Less severe effects of alcohol use during pregnancy include mild to moderate mental and physical growth retardation, referred to as Foetal Alcohol Effects (FAE) (Sanchez 1979). Furthermore as many as 5% of all congenital anomalies have been attributed to prenatal alcohol exposure (Pietrantoni 1991). Children of women who consume alcohol can also be at risk of reduced developmental goal attainment as a result of either a direct effect of the exposure or from the associated lifestyle factors connected to alcohol use (Belcher 1999; Eriksson 2000; Faden 2000; Frank 2001; Jacobson 2002; Singer 2002). Increased child abuse and neglect have been documented in some populations as a result of alcohol use during pregnancy (Bessinger 1999; Nair 1997) along with child deaths (Jaudes 1997). Furthermore mother‐infant attachment and responsiveness is compromised by alcohol use during pregnancy, along with post‐natal depression and possible domestic violence within the household. Finally mothers who consume alcohol are less likely to attend health facilities for education and medical treatment (Doggett 2005).
Description of the intervention
There are many pharmacologic treatments available to assist with alcohol treatment. These drugs are given to both lessen the effects during the withdrawal period and to help maintain abstinence. They are most commonly used in more severe cases of alcoholism. Drugs given during detoxification include Benzodiazepines (BZs), phenothiazines and chlormethiazone among others (Mann 1996). These drugs protect against the medical morbidity and mortality associated with withdrawal. Benzodiazepines in particular protect against seizures which are caused by autonomic instability secondary to withdrawal. In addition these medicines suppress the patient's anxiety and insomnia and increase the chances of completing detoxification.
In addition to the drugs listed above, anti‐depressants have also been used in the post‐withdrawal phase. However only three drugs have been approved by the United States Federal Drug Administration (FDA) for the treatment of alcohol dependence and abuse following detoxification; disulfiram, naltrexone and acamprosate (FDA 2007, Jaffe 1992). Each drug uses a different mechanism of action to influence alcohol abstinence. Disulfiram works by causing an adverse reaction with the consumption of alcohol; naltrexone attenuates the "high" of alcohol consumption; and acamprosate decreases the cravings for alcohol in abstinent alcohol dependent persons (Mann 1996, Kenna, 2004, Kenna 2004a). Naltrexone and acamprosate have been shown to be effective in reducing the frequency of drinking days and increasing the time to relapse and time to first drink (Garbutt 1999, Kranzler 2001). Although disulfiram is the oldest of the medications, trials have shown inconclusive results on the drug’s overall effectiveness. It does appear to be useful in delaying time to first drink from fear of the reaction (Garbutt 1999) but not necessarily effective in long term abstinence from alcohol (Kranzler 2001). Although much of the published literature includes both males and females there is little specific evidence for the effectiveness of any of these treatments in pregnancy. Each of these drugs holds a class C pregnancy category in the US which means that there is evidence of adverse effects in animal studies but no adequate or well‐controlled human studies (FDA 2007). In Australia they hold either a B2 or B3 category which means that “the drugs have been taken by a small number of pregnant women with no increase in the frequency of malformation or harmful effects to the foetus and studies in animals have shown evidence of harmful effects but the correlation to humans is uncertain (TGA 2007 , FDA 2007 ). In short, the effectiveness of these drugs in pregnancy has not been fully ascertained. Due to the short duration of pregnancy and the importance of this time period, it may be especially important to find treatments that work effectively, even for short periods of time.
How the intervention might work
Specific interventions need to be put in place to assist pregnant women and postpartum women who have alcohol problems. Interventions should be aimed at harmful alcohol use, pregnancy care, health surveillance and promotion, counselling, social support, education, facilitation of mother‐infant interaction and promotion of parenting (Doggett 2005). Such interventions should facilitate earlier and more intensive pregnancy care, improve pregnancy and neonatal outcomes, reduce alcohol use, aid in mother‐infant interaction and improve the home environment. Ideally these interventions would improve longer‐term outcomes such as reducing child neglect, reducing mother‐infant separation, improving neurodevelopment outcomes, increasing successful schooling performance and decreasing problems in adolescence and young adulthood (Olds 2002).
Why it is important to do this review
Effective interventions are needed and need to be evaluated among pregnant women in alcohol treatment in order to reduce the number of infant born with foetal alcohol syndrome. A systematic review is necessary in this area as, to our knowledge, there are none to date. There is a parallel Cochrane review on Psychosocial interventions for women enrolled in alcohol treatment during pregnancy (Lui 2008) but none on pharmacological therapies.
Objectives
This review examined the effectiveness of pharmacologic treatments in pregnant women enrolled in alcohol treatment programmes when compared to other pharmacologic treatments, placebo, non‐intervention, psychosocial interventions.
Methods
Criteria for considering studies for this review
Types of studies
We sought to review all randomised controlled trials (RCTs) or quasi random methods of participant allocation.
Types of participants
Trials that enrolled pregnant or postpartum women in alcohol treatment programmes were to be included in this review. No minimum level of alcohol use was required for inclusion, so long as the authors stated the women were receiving alcohol treatment. Studies were excluded if the participants were illicit drug (i.e. cannabis, heroin, cocaine, amphetamine etc) users and were treated for their illicit substance use disorders. Studies that did not report participants' alcohol use were not included.
Types of interventions
Experimental intervention:
This review sought to include any pharmacologic treatments used for the treatment of alcohol dependence. In order to be eligible, a study must include at least one group where only a pharmacologic treatment was given.
Control Intervention:
This review compared the experimental intervention to: other pharmacologic treatment alone or in association with psychosocial treatment, placebo, non‐intervention, psychosocial intervention alone
Types of outcome measures
Each trial must, at minimum, must report at least birth, abstinence and retention outcomes
Primary outcomes
Birth outcomes:
birth weight.
gestational age at birth.
placental abruption.
foetal alcohol syndrome (FAS).
admission to and length of time spent in hospital (i.e. neonatal intensive care unit [NICU]).
Secondary outcomes
Abstinence outcomes:
alcohol abuse measured by: maternal toxicology, maternal self‐report, newborn toxicology and any biological markers provided in the original studies.
Retention outcomes
treatment attendance as measured by the proportion or count of treatment visits attended.
treatment attendance as measured by the proportion or count of individuals who complete treatment.
prenatal care attendance as measured by the proportion or count of prenatal visit attended.
Search methods for identification of studies
We undertook both electronic and manual searches to identify the studies of review.
Electronic searches
We searched the following databases:
Cochrane Drug and Alcohol Group trials register (August 2008)
MEDLINE (1950 to August 2008)
EMBASE (1974 to August 2008)
CINAHL (1982 to August 2008)
PsycINFO (1806 to August 2008)
Search strategies for each database can be found in the appendices (Appendix 1, Appendix 2, Appendix 3, Appendix 4). Each search was based on the MEDLINE search strategy (Host: Dialog DataStar) developed in conjunction with a librarian (Leeds Partnership Foundation Trust). We did not apply any language restriction to the review.
Searching other resources
We searched:
the reference lists of all relevant papers to identify further studies.
some of the main electronic sources of ongoing trials (Current controlled trials meta register of controlled trials (mRCT); clinicaltrials.gov; The International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) Clinical trials portal: www.ifpma.org/clinicaltrials.html).
conference proceedings likely to contain trials relevant to the review. We contact investigators seeking information about unpublished or incomplete trials.
All searches included non‐English language literature and studies with English abstracts were assessed for inclusion. When considered likely to meet inclusion criteria, studies were translated.
Data collection and analysis
Selection of studies
Two reviewers read all titles and/or abstracts resulting from the search process and eliminated any irrelevant studies. We obtained full copies of all the potentially relevant studies. Two reviewers acting independently classified these as included, excluded or unclear. Decisions were based upon inclusion criteria outlined in the protocol. Differences in opinion were resolved through consensus or referral to a third reviewer.
Data extraction and management
Data was to be extracted by two reviewers independently using a data‐extraction form that will be developed to assess the following data: study location, methods, participant details, type of intervention, and outcomes.
Assessment of risk of bias in included studies
The reviewers were to assess the methodological quality of included studies as per Cochrane Handbook for Systematic Reviews for Interventions (Higgins 2008). Appraisal of the included studies was carried out independently by two reviewers. Any differences were to be negotiated by a third reviewer to reach consensus. We evaluated the included studies as follow:
A. Sequence generation was to be assessed for all outcomes. Studies were considered at low risk of bias if they provided a clear method of generating an allocation sequence to produce comparable groups, i.e. random number table, computer random number generator, coin tossing, shuffling cards or envelopes, throwing dice. Studies were considered at high risk of bias if they used some systematic, non‐random approach, i.e. date of birth, date of admission, clinic record number, by clinician.
B. Allocation concealment was to be assessed for all outcomes. Studies were considered at low risk of bias if they provided adequate allocation concealment, i.e. central allocation including telephone, web‐based, and pharmacy‐controlled, randomization; sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes. Studies were determined at high risk of bias if they had inadequate allocation concealment, i.e. using an open random allocation schedule such as a list of random numbers; assignment envelopes were used without appropriate safeguards e.g. if envelopes were unsealed or non‐opaque or not sequentially numbered; alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure.
C. Blinding of participants, personnel, and outcome assessor was to be considered separately for objective outcomes (discontinuation rates) and subjective outcomes (global state, craving, and withdrawal symptoms). For discontinuation rates, we judged that lack of blinding was unlikely to influence data collection.
D. Incomplete outcome data were to be considered for all outcomes except for discontinuation rates. It was assessed for results at the end of the study period. Studies were considered at low risk of bias if they adequately addressed missing data.
E. Selective outcome reporting was to be considered for all outcomes except for discontinuation rates.
Studies were to be judged to have unclear risk of bias if there was insufficient information to permit judgment of 'low' or 'high' risk of bias for each of the domains.
Measures of treatment effect
Dichotomous outcomes were to be analysed calculating the Relative risk (RR) for each trial with the uncertainty in each result being expressed by their confidence intervals. Continuous outcomes were to be analysed by calculating the WMD (weighted mean difference) with 95%CI.
Unit of analysis issues
Although none was available we had not planned to use data presented as number of positive urine tests over total number of tests in the experimental and control group as a measure of alcohol use. This is because using tests instead of the participants as the unit of analysis violates the hypothesis of independence among observations. As multiple urine tests would likely have been done in an individual patient, a urine test would not have been an appropriate unit of analysis.
Dealing with missing data
In this study population it is plausible to assume there would have been missing information for participants for different study points. Therefore a sensitivity analysis would have been performed. We were not going to exclude studies based on missing data for study subjects, as retention was one of the outcomes of interest for this review.
Assessment of heterogeneity
Due to the nature of the studies in this review, it was anticipated that there would be some degree of heterogeneity in the study interventions, outcome measures reported and methodological quality. Therefore pooling of the results may not have always been appropriate. We planned to use a p‐value of the chi‐square test less than 0.05 in the assessment of heterogeneity.
Assessment of reporting biases
Funnel plots were to be used to assess the potential for bias related to both trial size and negative versus positive outcomes, evidence of publication bias
Data synthesis
We planned to perform meta‐analysis and narrative review where appropriate for each of the nominated outcomes. Where possible, we planned to pool results of similar studies. The RR or the WMD from the individual trials were to be combined through meta‐analysis using a fixed effect model unless there was significant heterogeneity, in which case a random effect model was to be used. A p‐value of the chi‐square test less than 0.05 was to indicate a significant heterogeneity.
The RevMan 5 software package was to be used to perform the meta‐analysis for continuous and dichotomous outcome measures.
Sensitivity analysis
The methodological assessments was not used as inclusion criteria for the review, but was to be described and discussed. Sensitivity analysis was to be used to assess the methodological quality of the results
Results
Description of studies
Results of the search
The search strategy identified 793 citations. Twenty‐three citations were deemed relevant for full text review, an additional ten articles were retrieved through hand searching references, for a total of thirty‐three articles. Following full text review no articles met the inclusion criteria. Data extraction and assessment of methodological quality were therefore not possible.
Included studies
We found no studies which met our inclusion criteria for this review.
Excluded studies
Thirty‐one of the retrieved for full text review were excluded because they were not the correct study design. A majority of the articles we found described cohorts, case series or case reports concerning the effects of drinking or pharmacologic interventions on the foetus. Many articles did not provide a control group with which to compare the results. Other articles were excluded because they were review articles. The references of these articles were searched for potentially relevant articles. Some of these reviews explained the limitations in implementing drug trials in pregnant women. See Characteristics of excluded studies
Risk of bias in included studies
Not applicable as no articles no articles met the inclusion criteria for this study.
Effects of interventions
Not applicable as no articles no articles met the inclusion criteria for this study.
Discussion
The main reason for study exclusion was study design, we found no randomised or quasi‐randomised control trials focused on pregnant women in alcohol treatment. We found case series, case reports or cohorts among women who had either used alcohol or pharmacologic treatments for alcohol use during their pregnancy. Many of these studies did not have a control group nor did they assess the efficacy of treatment for maternal abstinence or harm reduction, rather they focused instead on foetal outcomes. For example, Flores‐Huerta (Flores‐Huerta 1992) assessed the effects on the newborn of ethanol consumption during the prenatal and postpartum periods using a prospective cohort of 94 women in Mexico. The 32 alcohol consuming participants in this study reportedly drank between 5 and 10 units of alcohol, in the form of a cultural drink pulque, a day. While this study found no significant difference in terms of mean birth weight, length or head circumference between drinking and non drinking mothers it did find significantly more offspring of drinking mothers ranked below the third percentile in birth weight and head circumference. mothers ranked below the third percentile in birth weight and head circumference. A second excluded study, Laegreid and colleagues assessed the effects of benzodiazepine use in pregnancy on birth outcomes by comparing benzodiazepine exposed births to infants exposed to other psychotropic drugs and those without drug exposure. It is important to note that the drug treatment was for any psychological issues and not necessarily alcohol treatment. In fact pregnant women were excluded if they were currently abusing alcohol or other drugs in addition to the use of benzodiazepine. The benzodiazepine exposed infants were found to have significantly lower birth weight for gestational age, as well as greater impairment on neurologic and behavioural exams at birth than the non‐exposed reference group (Laegreid 1992a). While these and other excluded studies may provide insight into the potential effects of alcohol use and pharmacologic interventions, they are not able to fully answer the research question of this review. Without an adequate control group or the ability to accurately control for potential confounders it is impossible to know if observed adverse events are attributable to the pharmacologic intervention, alcohol use or another unknown reason. We did not find any articles examining maternal abstinence outcomes with the use of pharmaceutical interventions.
As has been stated in other reviews of the subject (Rayburn 2004, Ryberg 2003, Schottenfeld 1995), given the rarity of outcomes it is difficult to adequately power studies to observe neonatal and development effects of pharmaceuticals in pregnant women. Rather it may be more appropriate to place treatment outcome studies in the context of the maternal life course and child development.
The clinical and obstetrical care surrounding alcohol use in pregnancy is difficult and complex; each clinician must weigh the effects of a drug on the mother's health and substance use against the potential harmful effects on her foetus. Clearly the availability of quality evidence would assist with ante‐partum decision making by both the physician and mother.
Summary of main results
This review assessed the effectiveness of pharmacologic interventions of pregnant women in alcohol treatment. After a comprehensive search of electronic databases and hand searching of all references we found no articles which met our inclusion criteria.
Overall completeness and applicability of evidence
Not applicable as no articles no articles met the inclusion criteria for this study
Quality of the evidence
Not applicable as no articles no articles met the inclusion criteria for this study.
Authors' conclusions
Implications for practice.
As there were no RCTs found to answer this question we can make no evidence based recommendations for practice.
Implications for research.
Our review has raised the question of whether randomised control trials are the most appropriate study design for use in the evaluation of ante‐partum alcohol use. The size of the population necessary to power such a study, particularly in terms of assessing adverse neonatal outcomes would be extremely large. Also the long time course of follow‐up needed to assess developmental outcomes is not amendable to a RCT design as it would be prohibitably expensive.
Furthermore as our prior review (Terplan 2007) noted, the population of pregnant women who participate in RCTs for drug and alcohol treatment is not representative of women who continue to use drugs and alcohol in pregnancy and who might benefit from interventions. The women enrolled in the RCTs of psychosocial interventions for illicit drug use in pregnancy were overwhelmingly poor and socially marginalized. Given the stigma attached to drug and alcohol use in pregnancy, recruitment for outcomes trials is likely to remain difficult and adversely affect generalizability.
Quality epidemiologic outcome research is needed due to the magnitude of suffering alcohol use has on the public’s health. As our review noted the poor quality of published observational trials, rather than pushing future research towards RCTs, we suggest that quality cohort studies with appropriate unexposed controls to assess potential confounders such as continued maternal alcohol use and socioeconomic variables would be more appropriate and cost effective.
History
Protocol first published: Issue 4, 2008 Review first published: Issue 3, 2009
| Date | Event | Description |
|---|---|---|
| 26 March 2009 | New search has been performed | became a review |
Acknowledgements
The Cochrane Drug and Alcohol group assisted greatly in the formulation of our review question and their assistance in editing the manuscript.
Appendices
Appendix 1. MEDLINE search strategy
SUBSTANCE?RELATED?DISORDERS.DE.
((DRUG OR SUBSTANCE) ADJ (ADDICT$3 OR ABUS$3 OR DEPENDEN$4)).TI,AB.
(INTOXICAT$3 OR ABSTINEN$2 OR WITHDRAW$3).TI,AB.
(EXCESSIVE$2 ADJ USE$3).TI,AB.(USE$3 ADJ DISORDER$2).TI,AB.
(DRINKING ADJ BEHAVI$3).TI,AB.
DRINKING?BEHAVIOR.DE.
ALCOHOL$3.TI,AB.
ALCOHOLISM.W..DE. OR ALCOHOL?DRINKING.DE. OR ALCOHOLISM.W..DE.
1 OR 2 OR 3 OR 4 OR 5 OR 6 OR 7 OR 8
PSYCHOPHARMACOLOGY.W..DE.
PHARMACOLOGY.W..DE.
PHARMACOLOG$4.TI,AB.
PHARMACOTHERAP$3.TI,AB.
BENZODIAZEPINES#.W..DE.
BENZODIAZEPINE.TI,AB.
ANTI ?ANXIETY?AGENTS#.DE.
ANXIOLYTIC.TI,AB.
HYPNOTICS AND SEDATIVES#.DE.
ANTIDEPRESSIVE?AGENTS#.DE. OR ANTIDEPRESSIVE?AGENTS SECOND?GENERATION#.DE. OR ANTIDEPRESSIVE?AGENTS? TRICYCLIC#.DE.
ANTIDEPRESS$4.TI,AB.
ANTICONVULSANTS#.W..DE.
SEROTONIN?UPTAKE?INHIBITORS#.DE.
ADRENERGIC?BETA?ANTAGONISTS#.DE.
ADRENERGIC?BETA?AGONISTS#.DE.
DISULFIRAM#.W..DE.
DISULFIRAM.TI,AB.
ACAMPROSATE.TI,AB.
NARCOTIC?ANTAGONISTS#.DE.
NALTREXONE.TI,AB.
PHENOTHIAZINES#.W..DE.
PHENOTHIAZINES.TI,AB.
CHLORMETHIAZONE.TI,AB.
MONOAMINE?OXIDASE?INHIBITORS.DE.
(MONOAMINE ADJ OXIDASE ADJ INHIBITOR).TI,AB.
10/34 OR
PREGNANCY#.W..DE.
PREGNAN$5.TI,AB.
PREGNANCY?COMPLICATIONS.DE.
(PREGNANCY ADJ COMPLICATIONS).TI,AB.
INFANT?NEWBORN.DE.
POSTPARTUM?PERIOD#.DE.
PRENATAL?DIAGNOSIS#.DE.
FETUS#.W..DE.
36 OR 37 OR 38 OR 39 OR 40 OR 41 OR 42 OR 43
PT=RANDOMIZED‐CONTROLLED TRIAL
PT=CONTROLLED‐CLINICALTRIAL
RANDOMIZED.TI,AB.
PLACEBO.TI,AB.
RANDOMLY.TI,AB.
GROUPS.TI,AB.
TRIAL.TI,AB.
45 OR 46 OR 47 OR 48 OR 49 OR 50 OR 51
52 AND HUMAN=YES
9 AND 35 AND 44 AND 53
Appendix 2. EMBASE search strategy
substance‐related disorders/
((drug or substance) adj (Addict$ or abus$ or dependen$)).mp
(intoxicat$ or abstinen$ or withdrawal$).mp.
(excessive$ adj use$).mp.
(use$ adj disorder$).mp.
(drinking adj behavi$3).mp.
drinking behavior.mp.
alcohol$.mp.
alcoholism/
(alcohol adj abuse).mp
1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10
psychopharmacology.mp.
pharmacolog*.mp.
pharmacotherap$3.mp.
benzodiazepine#.mP
benzodiazepine.mp
anti‐anxiety agent$.mp.
anxiolytic.mp.
(hypnotics and sedative$).mp.
antidepressive agent$1.mp.
antidepressive agent$1 second generation.mp.
antidepressive agent$1 tricyclic.mp.
antidepress$4.mp.
anticonvulsants.mp.
serotonin uptake inhibitors.mp.
adrenergic beta antagonists.mp.
adrenergic beta agonists/
disulfiram.mp.
disulfiram/
acamprosate.mp.
lithium.mp.
12/31 OR
pregnancy/
pregnan$5.mp.
pregnancy complications/
(pregnancy adj complications).mp.
infant newborn/
postpartum period/
prenatal diagnosis/
fetus.mp.
33 or 34 or 35 or 36 or 37 or 38 or 39 or 40
randomised controlled trial.mp.
randomised controlled trial/
control trial.mp.
random allocation.mp.
double blind method.mp.
single blind method.mp.
clinical trial/
(clin$ adj trial).mp.
clinical trial.mp.
((singl$ or doubl$ or trbl$) adj (blind or mask$)).mp.
plaCEBO/
placebo$.mp.
randomis$.mp.
research design.mp.
42/55 OR
11 and 32 and 41 and 56
Appendix 3. PsycInfo search strategy
Addiction#.W..DE. OR Alcoholism#.W.DE.
(drug OR substance).TI,AB. AND (addict$4 OR abus$3 OR dependen$3 OR misuse$3).TI,AB.
(overdos$4 OR intoxicat$4OR abstinen$3 OR withdraw$3OR relaps$2).TI,AB.
(excessive$2 ADJ use$3).TI,AB.
(use$4 ADJ disorder$4).TI,AB.
Drinking?Behavior#.DE.
Alcoholism#.W.DE.
Alcohol?Abuse#.DE.
1 or 2 or 3 or 4 or 5 or 6 or 7 or 8
Pregnancy#.W..DE.
pregnan$5.TI,AB.
pregnan$4 ADJ complication$2
(Infant ADJ newborn).TI,AB.
Postpartum?Depression#.DE. OR Postpartum?Psychosis#.DE.
(postpartum ADJ period).TI,AB.
Prenatal?Diagnosis#.DE.
Fetus#.W..DE.
1 OR 2 OR 3 OR 4 OR 5 OR 6 OR 7 OR 8
Psychopharmacology#.W..DE.
Pharmacology#.W..DE.
pharmacolog$4.TI,AB.
pharmacotherap$3.TI,AB.
Benzodiazepines#.W..DE.
benzodiazepine$2.TI,AB.
Tranquilizing?Drugs#.DE.
(anti‐anxiety ADJagents).TI,AB.
(antianxiety ADJagents).TI,AB.
anxiolytic.TI,AB.
(hypnotics ADJ sedatives).TI,AB.
antidepress$4.TI,AB.
anticonvulsants.TI,AB.
Serotonin#.W..DE. OR
Serotonin?Reuptake? Inhibitors#.DE.
Adrenergic?Blocking?Drugs#.DE. OR Adrenergic?Drugs#.DE.
disulfiram.TI,AB.
Disulfiram#.W..DE.
acamprosate.TI,AB.
Narcotic?Agonists#.DE. OR Narcotic?Antagonists#.DE. OR Narcotic?Drugs#.DE.
naltrexone.TI,AB.
phenothiazines.TI,AB.
chlormethiazone.TI,AB.
Monoamine?Oxidase Inhibitors#.DE.
(monoamine ADJ oxidase ADJinhibitors).TI,AB.
19/43 OR
random$9.TI,AB.
random$9.TI,AB.
Placebo#.W..DE.
placebo.TI,AB.
Clinical?Trials#.DE.
(clinical ADJtrials).TI,AB
((singl$6 OR doubl$3 OR trebl$3 OR tripl$3) ADJ(blind$2 OR mask$3 OR stud$4)).TI,AB.
45 or 46 or 47 or 48 or 49 or 50 or 51
27/50 OR
9 AND 18 AND 44 AND 53
Appendix 4. CINAHL search strategy
Substance?Use?Disorders#.DE.
((drug OR substance) ADJ (addict$3 OR abus$4 OR dependen$3)).TI,AB.
(overdos$3 OR intoxicat$3 OR abstin$3 OR withdrawal$2 OR relaps$2).TI,AB.
(excessive$2 ADJ use$3).TI,AB.
(use$3 ADJ disorder$2).TI,AB.
(drinking ADJ behavi$5).TI,AB.
Drinking?Behavior#.DE.
alcohol$4.TI,AB.
Alcoholism#.W..DE. Alcohol?Abuse.DE. OR Alcoholism.W..DE. OR Alcoholism.W..DE. OR Alcoholism.W..DE.
1/9 OR
Psychopharmacology#.W..DE.
Pharmacy and Pharmacology.DE. OR Pharmacy and Pharmacology.DE.
pharmacolog$4.TI,AB.
pharmacotherap$3.TI,AB.
Antianxiety?Agents Benzodiazepine#.DE.benzodiazepine.TI,AB.
Antianxiety?Agents#.DE.anxiolytic.TI,AB.
Hypnotics and Sedatives#.DE.
Antidepressive?Agents#.DE. OR Antidepressive?Agents Second‐Generation#.DE. OR Antidepressive?Agents Tricyclic#.DE.
antidepress$4.TI,AB.
Anticonvulsants#.W..DE.
Serotonin?Uptake Inhibitors#.DE.
Adrenergic?Beta Agonists#.DE.
Disulfiram.W..DE.disulfiram.TI,AB.
acamprosate.TI,AB.
Narcotic?Antagonists#.DE.
naltrexone.TI,AB.
Antipsychotic?Agents?Phenothiazine#.DE.
phenothiazines.TI,AB.
chloromethiazone.TI,AB.
Monoamine‐Oxidase Inhibitors#.DE.
(monoamine ADJ oxidase ADJ inhibitor).TI,AB.
11/31
PREGNANCY#.W..DE.
PREGNAN$4.TI,AB.
33 OR 34
(CLINIC$2 ADJ TRIAL$2).TI,AB.
DOUBLE?BLIND?STUDIES#.DE. OR SINGLE?BLIND?STUDIES#.DE. OR TRIPLE? BLIND STUDIES#.DE.
CLINICAL?TRIALS#.
RANDOM?ASSIGNMENT#.DE.
META?ANALYSIS#.DE.
ALLOCAT$4.TI,AB.
CLIN$4.TI,AB.
RANDOM$4.TI,AB.
TRIAL$4.TI,AB.
36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44
10 and 32 and 33 and 45
Characteristics of studies
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
|---|---|
| Bartu 2006 | Substance treatment for illicit drugs, not alcohol. |
| Bergman 1992 | Study design not randomised control trial. |
| Brewer 2008 | Study design not randomised control trial. |
| Ferreira 2007 | Study design not randomised control trial; not in alcohol treatment. |
| Flores‐Huerta 1992 | Study design not randomised control trial; not in alcohol treatment. |
| Fuller 2004 | Study design not randomised control trial, opinion. |
| Heading 2008 | Study design not randomised control trial, review article, not pregnant women. |
| Kanto 1982 | Study design not randomised control trial, review article, participants not in alcohol treatment. |
| Laegreid 1992 | Study design not randomised control trial, not in alcohol treatment. |
| Laegreid 1992a | Study design not randomised control trial, not in alcohol treatment. |
| Lewis 1979 | Study design not randomised control trial, letter to the editor. |
| Lingford‐Hughes 2004 | Study design not randomised control trial, review, not stratified by pregnancy status. |
| Loebstein 1997 | Study design not randomised control trial, participants not in alcohol treatment. |
| Maier 1997 | Study design not randomised control trial, not in alcohol treatment. |
| Matalon 2002 | Study design not randomised control trial, not in alcohol treatment. |
| Mattison 2006 | Study design not randomised control trial, review article, participants not in alcohol treatment. |
| Mattson 2006 | Study design not randomised control trial, not in alcohol treatment. |
| Noland 2003 | Study design not randomised control trial, not in alcohol treatment. |
| Nora 1977 | Study design not randomised control trial. |
| Ornoy 1998 | Study design not randomised control trial. |
| Ostrea 2006 | Study design not randomised control trial, not in alcohol treatment. |
| Ramkisson 2008 | Study design not randomised control trial, not in alcohol treatment. |
| Rayburn 2004 | Study design not randomised control trial, review article. |
| Reitnauer 1997 | Study design not randomised control trial. |
| Rosenberg 1983 | Study design not randomised control trial. |
| Ryberg 2003 | Study design not randomised control trial, review article. |
| Scanlon 1975 | Study design not randomised control trial, letter to the editor. |
| Schottenfeld 1995 | Study design not randomised control trial, review. |
| Stuppaeck 1992 | Population not pregnant women. |
| Vocci 1995 | Study design not randomised control trial, review. |
| Vocci 2005 | Study design not randomised control trial, not in pregnancy. |
| Wozniak 2006 | Study design not randomised control trial, not in alcohol treatment. |
| Wright 2001 | Study design not randomised control trial, review article. |
Differences between protocol and review
The methodological quality of included studies was updated from the protocol, according to the new recommendation reported in the Cochrane Handbook.
Contributions of authors
ES contributed to the conception, design and development of the protocol; identified, extracted and entered data, participated in the review and interpretation of the results and drafted and edited the manuscript.
SL contributed to the conception, design and development of the protocol and search strategy for the review, identified and extracted and entered data, interpreted the results and contributed to the revision of the manuscript.
MT contributed to the conception, design and development of the protocol, identified, extracted and entered data, participated in the review and interpretation of the results and to the drafting and revision of the manuscript.
Declarations of interest
The authors report no conflict of interest.
New
References
References to studies excluded from this review
Bartu 2006 {published data only}
- Bartu A, Sharp J, Ludlow J, Doherty DA. Postnatal home visiting for illicit drug‐using mothers and their infants: a randomised controlled trial. Australian & New Zealand Journal of Obstetrics & Gynaecology 2006;46(5):419‐26. [DOI] [PubMed] [Google Scholar]
Bergman 1992 {published data only}
- Bergman U, Rosa FW, Baum C, Wiholm BE, Faich GA. Effects of exposure to benzodiazepine during fetal life. Lancet 1992;340(8821):694‐6. [DOI] [PubMed] [Google Scholar]
Brewer 2008 {published data only}
- Brewer C. Harm‐reduction for unwanted pregnancies and unwanted addictions: an instructive analogy. Adicciones 2008;20(1):5‐13. [PubMed] [Google Scholar]
Ferreira 2007 {published data only}
- Ferreira E, Carceller AM, Agogue C, Martin BZ, St‐Andre M, Francoeur D, et al. Effects of selective serotonin reuptake inhibitors and venlafaxine during pregnancy in term and preterm neonates. Pediatrics 2007;119(1):52‐9. [DOI] [PubMed] [Google Scholar]
Flores‐Huerta 1992 {published data only}
- Flores‐Huerta S, Hernandez‐Montes H, Argote RM, Villalpando S. Effects of ethanol consumption during pregnancy and lactation on the outcome and postnatal growth of the offspring. Annals of Nutrition & Metabolism 1992;36(3):121‐8. [DOI] [PubMed] [Google Scholar]
Fuller 2004 {published data only}
- Fuller RK, Gordis E. Does disulfiram have a role in alcoholism treatment today?[see comment]. [Review] [23 refs]. Addiction 2004;99(1):21‐4. [DOI] [PubMed] [Google Scholar]
Heading 2008 {published data only}
- Heading CE. Gender issues and the pharmacotherapy of substance abuse. [Review] [8 refs]. Idrugs 2008;11(6):428‐32. [PubMed] [Google Scholar]
Kanto 1982 {published data only}
- Kanto JH. Use of benzodiazepines during pregnancy, labour and lactation, with particular reference to pharmacokinetic considerations. [Review] [117 refs]. Drugs 1982;23(5):354‐80. [DOI] [PubMed] [Google Scholar]
Laegreid 1992 {published data only}
- Laegreid L, Hagberg G, Lundberg A. Neurodevelopment in late infancy after prenatal exposure to benzodiazepines‐‐a prospective study. Neuropediatrics 1992;23(2):60‐7. [DOI] [PubMed] [Google Scholar]
Laegreid 1992a {published data only}
- Laegreid L, Hagberg G, Lundberg A. The effect of benzodiazepines on the fetus and the newborn. Neuropediatrics 1992;23(1):18‐23. [DOI] [PubMed] [Google Scholar]
Lewis 1979 {published data only}
- Lewis PJ, Boylan P. Alcohol and fetal breathing. Lancet 1979;1(8112):388. [DOI] [PubMed] [Google Scholar]
Lingford‐Hughes 2004 {published data only}
- Lingford‐Hughes AR, Welch S, Nutt DJ, British Association for Psychopharmacology. Evidence‐based guidelines for the pharmacological management of substance misuse, addiction and comorbidity: recommendations from the British Association for Psychopharmacology. Journal of Psychopharmacology 2004;18(3):293‐335. [DOI] [PubMed] [Google Scholar]
Loebstein 1997 {published data only}
- Loebstein R, Koren G. Pregnancy outcome and neurodevelopment of children exposed in utero to psychoactive drugs: the Motherisk experience. [Review] [21 refs]. Journal of Psychiatry & Neuroscience 1997;22(3):192‐6. [PMC free article] [PubMed] [Google Scholar]
Maier 1997 {published data only}
- Maier SE, Chen WJ, Miller JA, West JR. Fetal alcohol exposure and temporal vulnerability regional differences in alcohol‐induced microencephaly as a function of the timing of binge‐like alcohol exposure during rat brain development. Alcoholism: Clinical & Experimental Research 1997;21(8):1418‐28. [DOI] [PubMed] [Google Scholar]
Matalon 2002 {published data only}
- Matalon S, Schechtman S, Goldzweig G, Ornoy A. The teratogenic effect of carbamazepine: a meta‐analysis of 1255 exposures. Reproductive Toxicology 2002;16(1):9‐17. [DOI] [PubMed] [Google Scholar]
Mattison 2006 {published data only}
- Mattison D, Zajicek A. Gaps in knowledge in treating pregnant women. [Review] [31 refs]. Gender Medicine 2006;3(3):169‐82. [DOI] [PubMed] [Google Scholar]
Mattson 2006 {published data only}
- Mattson SN, Calarco KE, Lang AR. Focused and shifting attention in children with heavy prenatal alcohol exposure. Neuropsychology 2006;20(3):361‐9. [DOI] [PMC free article] [PubMed] [Google Scholar]
Noland 2003 {published data only}
- Noland JS, Singer LT, Arendt RE, Minnes S, Short EJ, Bearer CF. Executive functioning in preschool‐age children prenatally exposed to alcohol, cocaine, and marijuana. Alcoholism: Clinical & Experimental Research 2003;27(4):647‐56. [DOI] [PMC free article] [PubMed] [Google Scholar]
Nora 1977 {published data only}
- Nora AH, Nora JJ, Blu J. Limb‐reduction anomalies in infants born to disulfiram‐treated alcoholic mothers. Lancet 1977;2(8039):664. [DOI] [PubMed] [Google Scholar]
Ornoy 1998 {published data only}
- Ornoy A, Arnon J, Shechtman S, Moerman L, Lukashova I. Is benzodiazepine use during pregnancy really teratogenic?. Reproductive Toxicology 1998;12(5):511‐5. [DOI] [PubMed] [Google Scholar]
Ostrea 2006 {published data only}
- Ostrea EM Jr, Hernandez JD, Bielawski DM, Kan JM, Leonardo GM, Abela MB, et al. Fatty acid ethyl esters in meconium: are they biomarkers of fetal alcohol exposure and effect?. Alcoholism: Clinical & Experimental Research 2006;30(7):1152‐9. [DOI] [PMC free article] [PubMed] [Google Scholar]
Ramkisson 2008 {published data only}
- Ramkisson R, Campbell M, Agius M. The clinical dilemma‐‐prescribing in pregnancy. Psychiatria Danubina 2008;20(1):88‐90. [PubMed] [Google Scholar]
Rayburn 2004 {published data only}
- Rayburn WF, Bogenschutz MP. Pharmacotherapy for pregnant women with addictions. [Review] [104 refs]. American Journal of Obstetrics & Gynecology 2004;191(6):1885‐97. [DOI] [PubMed] [Google Scholar]
Reitnauer 1997 {published data only}
- Reitnauer PJ, Callanan NP, Farber RA, Aylsworth AS. Prenatal exposure to disulfiram implicated in the cause of malformations in discordant monozygotic twins. [Review] [35 refs]. Teratology 1997;56(6):358‐62. [DOI] [PubMed] [Google Scholar]
Rosenberg 1983 {published data only}
- Rosenberg L, Mitchell AA, Parsells JL, Pashayan H, Louik C, Shapiro S. Lack of relation of oral clefts to diazepam use during pregnancy. New England Journal of Medicine 1983;309(21):1282‐5. [DOI] [PubMed] [Google Scholar]
Ryberg 2003 {published data only}
- Ryberg U. Pregnancy, Neonatal Period and Substance Abuse. In: Berglund M, Thelander S, Jonsson E editor(s). Treating alcohol and drug abuse: An evidence based review.. Vol. 1, Weinheim, Germany: Wiley, 2003:Chp 10, 573‐582. [Google Scholar]
Scanlon 1975 {published data only}
- Scanlon JW. Letter: Effect of benzodiazepines in neonates. New England Journal of Medicine 1975;292(12):649‐50. [DOI] [PubMed] [Google Scholar]
Schottenfeld 1995 {published data only}
- Schottenfeld R S. Clinical trials of pharmacologic treatments in pregnant women‐‐methodologic considerations.. NIDA‐Research Monograph. Rockville, MD: NIH, 1995, issue 149‐1995:201. [PubMed]
Stuppaeck 1992 {published data only}
- Stuppaeck CH, Pycha R, Miller C, Whitworth AB, Oberbauer H, Fleischhacker WW. Carbamazepine versus oxazepam in the treatment of alcohol withdrawal: a double‐blind study. Alcohol & Alcoholism 1992;27(2):153‐8. [PubMed] [Google Scholar]
Vocci 1995 {published data only}
- Vocci F. Overview: Medications Development for the Treatment of Drug Abuse. NIDA‐Research Monograph. Rockville, MD: NIH, 1995, issue 149:4. [PubMed]
Vocci 2005 {published data only}
- Vocci F, Ling W. Medications development: successes and challenges. Pharmacology & Therapeutics 2005;108(1):94‐108. [DOI] [PubMed] [Google Scholar]
Wozniak 2006 {published data only}
- Wozniak JR, Mueller BA, Chang PN, Muetzel RL, Caros L, Lim KO. Diffusion tensor imaging in children with fetal alcohol spectrum disorders. Alcoholism: Clinical & Experimental Research 2006;30(10):1799‐806. [DOI] [PMC free article] [PubMed] [Google Scholar]
Wright 2001 {published data only}
- Wright A, Walker J. Drugs of abuse in pregnancy. [Review] [54 refs]. Best Practice & Research in Clinical Obstetrics & Gynaecology 2001;15(6):987‐98. [DOI] [PubMed] [Google Scholar]
Additional references
AAP 2000
- AAP. American Academy of Pediatrics. Committee on substance abuse and committee on children with disabilities. Fetal alcohol syndrome and alcohol related neruodevelopmental disorders.. Pediatrics 2000;106:358‐61. [PubMed] [Google Scholar]
Barrison 1985
- Barrison IG, Waterson EJ, Murray‐Lyon IM. Adverse effects of alcohol in pregnancy. British Journal of Addiction 1985;80:11‐22. [DOI] [PubMed] [Google Scholar]
Belcher 1999
- Belcher HM, Shapiro BK, Leppert M, Butz AM, Sellers S, Arch E, et al. Sequential neuromotor examination in children with intrauterine cocaine / polydrug exposure. Developmental Medicine and Children Neurology 1999;41(4):240‐6. [DOI] [PubMed] [Google Scholar]
Bessinger 1999
- Bessinger BA, Garland AF, Litrownik AJ, Landsverk JS. Caregiver substance abuse among maltreated children placed in out‐of‐home care. Child Welfare 1999;78:221‐39. [PubMed] [Google Scholar]
Doggett 2005
Eriksson 2000
- Eriksson M, Jonsson B, Steneroth G, Zetterstrom R. Amphetamine abuse during pregnancy: environmental factors and outcomes after 14‐15 years. Scandinavian Journal of Public Health 2000;28:154‐7. [DOI] [PubMed] [Google Scholar]
Faden 2000
- Faden VB, Graubard BI. Maternal substance use during pregnancy and developmental outcomes at age three. Journal of substance Abuse Treatment 2000;12:329‐40. [DOI] [PubMed] [Google Scholar]
FDA 2007
- Annomyous. Center for Drug Evaluation and Research, Label and History. US Food and Drug Administration Acessed Dec 15, 2007:www.fda.gov.
Frank 2001
- Frank DA, Augustyn M, Knight WG, Pell T, Zuckerman B. Growth, development, and behavior in early childhood following prenat. JAMA 2001;285:1613‐25. [DOI] [PMC free article] [PubMed] [Google Scholar]
Garbutt 1999
- Garbutt, James, West SL, Carey TS, Lohr KN, Crew FT. Pharmacological Treatment of Alcohol Dependence A Review of the Evidence. JAMA April 1999;281(14):1318‐25. [DOI] [PubMed] [Google Scholar]
Higgins 2008
- Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1. The Cochrane Collaboration, 2008 [updated September 2008]; Vol. Available from www.cochrane‐handbook.org..
ICAP 2007
- International Center for Alcohol Policies. International Guidelines on Drinking and Pregnancy International Guidelines on Drinking during Pregnancy. Policy Issues, Drinking Guidelines October 15, 2007; Vol. www.icap.org.
Jacobson 2002
- Jacobson SW, Chiodo LM, Sokol RJ, Jacobson JL. Validity of maternal report of prenatal alcohol, cocaine and smoking relation to neurbehavioral outcomes. Pediatrics 2002;109:815‐25. [DOI] [PubMed] [Google Scholar]
Jaffe 1992
- Jaffe, Jerone, Kranzler HR, Ciraulo DA. Drugs Used in the Treatment of Alcoholism. In: Mendelson, Jack H. Mello, Nancy K editor(s). Medical Diagnosis and Treatment of Alcoholism. New York: McGraw‐ Hill INC, 1992:421‐62. [Google Scholar]
Jaudes 1997
- Jaudes PK, Ekwo EE. Outcomes for infants exposed in utero to illict drugs. Child Welfare 1997;76:521‐34. [PubMed] [Google Scholar]
Kenna 2004a
- Kenna, George, McGeary John, Swift Robert. Pharmacotherapy, pharmacogenomics and the future of Alcohol Dependence, part 2. Am J Health‐Syst Pharm 2004;61:2280‐8. [Google Scholar]
Kenna, 2004
- Kenna, George, McGeary John, Swift Robert. Pharmacotherapy, pharmacogenomics and the future of alcohol dependence treatment, part 1. Am J Health‐Syst Pharm 2004;61:2272‐9. [DOI] [PubMed] [Google Scholar]
Kranzler 2001
- Kranzler HR, VanKirk J. Efficacy of Naltrexone and Acamprostate for Alcoholism Treatment: A Meta‐Analysis. Alcoholism:Clinical and Experimental Research September 2001;25(9):1335‐41. [PubMed] [Google Scholar]
Lui 2008
- Lui S, Terplan M, Smith EJ. Psychosocial interventions for women enrolled in alcohol treatment during pregnancy. Cochrane Database of Systematic Reviews 2008, Issue 3. [DOI: 10.1002/14651858.CD006753.pub2] [DOI] [PubMed] [Google Scholar]
Mann 1996
- Mann, Karl. The Pharmacological Treatment of Alcohol Dependence: Needs and Possibilities. Alcohol & Alcoholism 1996;31(Suppl 1.):55‐8. [PubMed] [Google Scholar]
Nair 1997
- Nair P, Black MM, Schuler M, Keane V, Snow L, Rigney BA, et al. Risk factors for disruption in primary caregiving among infants of substance abusing women. Child Abuse and Neglect 1997;21:1039‐51. [DOI] [PMC free article] [PubMed] [Google Scholar]
NICE 2008
- National Collaborating Centre for Womens and Children's Health. Antenatal care: routine care for the healthy pregnant woman. NICE clinical guideline 62 March 2008:18.
NSDUH 2006
- Substance Abuse and Mental Health Service Adminstration. Summary of findings from the 2006 National Survey on Drug Use & Health. Office of Applied Studies. Vol. NSDUH series, Rockville, MD: DHHS Publication, 2006:13. [Google Scholar]
NSDUH 2007
- Substance Abuse and Mental Health Service Administration. Results from the 2006 National Survey on Drug Use and Health:National Findings. Office of Applied Studies. NSDUH Series H‐32, 3. Rockville, MD.: DHHS Publication No. SMA 07‐429, 2007.
Olds 2002
- Olds DL, Robinson J, O'Brien R, Luckey DW, Pettitt LM, Henderson CR Jr, et al. Home visiting by paraprofessionals and by nurses: a randomised controlled trial. Pediatrics 2002;110:486‐96. [DOI] [PubMed] [Google Scholar]
ONS 2006
- National Statistics. Statistics on alcohol: England 2006. National Statistics 2006:39.
Pietrantoni 1991
- Pietrantoni M, Knuppel RA. Alcohol use in pregnancy. Clinical Perinatology 1991;18:93‐111. [PubMed] [Google Scholar]
Raistrick 2006
- Raistrick D, Heather N, Godfrey C. Review of the effectiveness of treatment for alcohol problems. National Treatment Agency for Substance Misuse 2006.
Sanchez 1979
- Sanchez SM, Mize SG, Jiminez JM, Monroe BL, Rosenfield CR, Tyson JE. Systems approach to evaluation of maternal and neonatal care. 12th Hawaiian International Conference on System Sciences. 1979.
Singer 2002
- Singer LT, Arendt R, Minnes S, Farkas K, alvator A, Kirchner HL, et al. Cognitive and motor outcomes of cocaine‐exposed infants. JAMA 2002;287:1952‐60. [DOI] [PMC free article] [PubMed] [Google Scholar]
Strategy Unit 2003
- Prime Minister's Strategy Unit. Alcohol Project : Interim Alaytical Report. Cabinet Office. London: UK Government, 2003. [Google Scholar]
Taylor 2006
- Taylor DJ. Alcohol consumption and outcomes of pregnancy. Statement No. 5. Royal College of Obstricians and Gynaecologist. London, 2006.
Terplan 2007
- Terplan M, Lui S. Psychosocial interventions for pregnant women in outpatient illicit drug treatment programs compared to other interventions. Cochrane Database of Systematic Reviews 2007, Issue 4. [DOI: 10.1002/14651858.CD006037.pub2.] [DOI] [PubMed] [Google Scholar]
TGA 2007 [Computer program]
- TGA 2007. http://www.tga.gov.au/docs/html/medpreg.htm. Commonwealth of Australia 1999, Last Updated: 14 February 2007; Vol. Accessed: Dec 15, 2007.
Weintraub 1998
- Weintraub Z, Bental Y, Olivan A, Rotschild A. Neonatal withdrawal syndrome and behavioral effects produced by maternal drug use. Addiction Biology 1998;2:159‐70. [DOI] [PubMed] [Google Scholar]