Brian J. Cleary

Early pregnancy azathioprine use and pregnancy outcomes

BACKGROUND Azathioprine (AZA) is used during pregnancy by women with inflammatory bowel disease (IBD), other autoimmune disorders, malignancy, and organ transplantation. Previous studies have demonstrated potential risks. METHODS The Swedish Medical Birth Register was used to identify 476 women who reported the use of AZA in early pregnancy. The effect of AZA exposure on pregnancy outcomes was studied after adjustment for maternal characteristics that could act as confounders. RESULTS The most common indication for AZA use was IBD. The rate of congenital malformations was 6.2% in the AZA group and 4.7% among all infants born (adjusted OR: 1.41, 95% CI: 0.98-2.04). An association between early pregnancy AZA exposure and ventricular/atrial septal defects was found (adjusted OR: 3.18, 95% CI: 1.45-6.04). Exposed infants were also more likely to be preterm, to weigh <2500 gm, and to be small for gestational age compared to all infants born. This effect remained for preterm birth and low birth weight when infants of women with IBD but without AZA exposure were used as a comparison group. A trend toward an increased risk of congenital malformations was found among infants of women with IBD using AZA compared to women with IBD not using AZA (adjusted OR: 1.42, 95% CI: 0.93-2.18). CONCLUSIONS Infants exposed to AZA in early pregnancy may be at a moderately increased risk of congenital malformations, specifically ventricular/atrial septal defects. There is also an increased risk of growth restriction and preterm delivery. These associations may be confounded by the severity of maternal illness.

Methadone dose and neonatal abstinence syndrome: systematic review and meta-analysis

AIM To determine if there is a relationship between maternal methadone dose in pregnancy and the diagnosis or medical treatment of neonatal abstinence syndrome (NAS). METHODS PubMed, EMBASE, the Cochrane Library and PsychINFO were searched for studies reporting on methadone use in pregnancy and NAS (1966-2009). The relative risk (RR) of NAS was compared for methadone doses above versus below a range of cut-off points. Summary RRs and 95% confidence intervals (CI) were estimated using random effects meta-analysis. Sensitivity analyses explored the impact of limiting meta-analyses to prospective studies or studies using an objective scoring system to diagnose NAS. RESULTS A total of 67 studies met inclusion criteria for the systematic review; 29 were included in the meta-analysis. Any differences in the incidence of NAS in infants of women on higher compared with lower doses were statistically non-significant in analyses restricted to prospective studies or to those using an objective scoring system to diagnose NAS. CONCLUSIONS Severity of the neonatal abstinence syndrome does not appear to differ according to whether mothers are on high- or low-dose methadone maintenance therapy.

Methadone and perinatal outcomes: a retrospective cohort study.

OBJECTIVE The purpose of this study was to examine the relationship among methadone maintenance treatment, perinatal outcomes, and neonatal abstinence syndrome. STUDY DESIGN This was a retrospective cohort study of 61,030 singleton births at a large maternity hospital from 2000-2007. RESULTS There were 618 (1%) women on methadone at delivery. Methadone-exposed women were more likely to be younger, to book late for antenatal care, and to be smokers. Methadone exposure was associated with an increased risk of very preterm birth <32 weeks of gestation (adjusted odds ratio [aOR], 2.47; 95% confidence interval [CI], 1.40-4.34), being small for gestational age <10th percentile (aOR, 3.27; 95% CI, 2.49-4.28), admission to the neonatal unit (aOR, 9.14; 95% CI, 7.21-11.57), and diagnosis of a major congenital anomaly (aOR, 1.94; 95% CI, 1.10-3.43). There was a dose-response relationship between methadone and neonatal abstinence syndrome. CONCLUSION Methadone exposure is associated with an increased risk of adverse perinatal outcomes, even when known adverse sociodemographic factors have been accounted for. Methadone dose at delivery is 1 of the determinants of neonatal abstinence syndrome.

Prevalence, predictors and perinatal outcomes of peri-conceptional alcohol exposure - retrospective cohort study in an urban obstetric population in Ireland

BackgroundEvidence-based advice on alcohol consumption is required for pregnant women and women planning a pregnancy. Our aim was to investigate the prevalence, predictors and perinatal outcomes associated with peri-conceptional alcohol consumption.MethodsA cohort study of 61,241 women who booked for antenatal care and delivered in a large urban maternity hospital between 2000 and 2007. Self-reported alcohol consumption at the booking visit was categorised as low (0-5 units per week), moderate (6-20 units per week) and high (>20 units per week).ResultsOf the 81% of women who reported alcohol consumption during the peri-conceptional period, 71% reported low intake, 9.9% moderate intake and 0.2% high intake. Factors associated with moderate alcohol consumption included being in employment OR 4.47 (95% CI 4.17 to 4.80), Irish nationality OR 16.5 (95% CI 14.9 to 18.3), private health care OR 5.83 (95% CI 5.38 to 6.31) and smoking OR 1.86 (95% CI 1.73 to 2.01). Factors associated with high consumption included maternal age less than 25 years OR 2.70 (95% CI 1.86 to 3.91) and illicit drug use OR 6.46 (95% CI 3.32 to 12.60). High consumption was associated with very preterm birth (<32 weeks gestation) even after controlling for socio-demographic factors, adjusted OR 3.15 (95% CI 1.26-7.88). Only three cases of Fetal Alcohol Syndrome were recorded (0.05 per 1000 total births), one each in the low, moderate and high consumption groups.ConclusionsPublic Health campaigns need to emphasise the importance of peri-conceptional health and pre-pregnancy planning. Fetal Alcohol Syndrome is likely to be under-reported despite the high prevalence of alcohol consumption in this population.

Prevalence and predictors of periconceptional folic acid uptake—prospective cohort study in an Irish urban obstetric population

BACKGROUND Neural tube defects (NTDs) are severe abnormalities of the central nervous system that occur as a result of abnormal development in the third and fourth weeks of gestation. Studies have shown that periconceptional folic acid (FA) can reduce both the incidence and recurrence of NTDs. METHODS A cohort study was carried out using the electronic hospital booking records of women delivering in a large Dublin maternity hospital between 2000 and 2007. Logistic regression analyses were performed to measure the associations between maternal factors and optimal FA use. RESULTS Of the 61,252 women in the cohort, 85% reported taking FA at some point during the periconceptional period; however, only 28% took FA as recommended. Factors associated with taking the recommended amount of FA included nulliparity [adjusted OR: 1.35 (95% CI: 1.28-1.43)], early booking (<12 weeks) [OR: 1.24 (95% CI: 1.17-1.31)], increasing maternal age (e.g. 30-34 years) [OR: 1.39 (95% CI: 1.30-1.48)], private health care [OR: 4.32 (95% CI: 4.1-4.6)] and fertility treatment [OR: 2.88 (95% CI: 2.44-3.40)]. Factors associated with taking less than recommended or no FA included unplanned pregnancy [OR: 0.08 (0.07-0.08)], lower socio-economic status (e.g. unemployed) [OR: 0.63 (95% CI: 0.55-0.71)], non-Irish nationality [OR: 0.82 (0.74-0.90)] and smokers [OR: 0.51 (95% CI: 0.47-0.55)]. CONCLUSIONS Social, demographic and economic factors have an important influence on the FA uptake. Vulnerable groups who report limited uptake of FA need to be specifically targeted in future Public Health campaigns and further consideration needs to be given to the debate on food fortification in countries where this is currently not available.

Medication use in early pregnancy‐prevalence and determinants of use in a prospective cohort of women

To examine the extent, nature and determinants of medication use in early pregnancy.

2009 A/H1N1 influenza vaccination in pregnancy: uptake and pregnancy outcomes – a historical cohort study

OBJECTIVES To describe the uptake of 2009 A/H1N1 influenza vaccination among pregnant women and determine if vaccination was associated with adverse pregnancy outcomes. STUDY DESIGN A historical cohort study was performed using booking, delivery suite and neonatal unit discharge records from the Coombe Women and Infants University Hospital, Dublin, Ireland. Singleton deliveries to women pregnant before (December 2008-September 2009) and during the pandemic (December 2009-September 2010) were included. Information on vaccination status and type of vaccine was collected on admission to the delivery suite. Logistic regression analyses were used to determine maternal characteristics associated with vaccination. Pregnancy outcomes were compared for vaccinated and unvaccinated women, with adjustment for differing maternal characteristics. Outcomes included vaccination status, preterm birth, size for gestational age, neonatal intensive care admission, congenital anomalies and perinatal death. RESULTS Of 6894 women pregnant during the pandemic, 2996 [43.5%] reported vaccination at delivery. In the early weeks of the vaccination programme rates of over 70% were achieved. Of those vaccinated, 246 [8.2%], 1709 [57.0%] and 1034 [34.5%] were vaccinated in the first, second and third trimesters respectively. Vaccination was less likely in younger age groups, those who were not in the professional/manager/employer socioeconomic group, women from Eastern Europe, Africa and Asia/Middle East, those who reported an unplanned pregnancy, women who booked late for antenatal care and recipients of publicly-funded obstetric care. Irish nationality was associated with reporting vaccination. There was no association between vaccination during pregnancy and adverse pregnancy outcomes. Women who were vaccinated were less likely to have a preterm delivery than unvaccinated women. CONCLUSION 2009 A/H1N1 influenza vaccination uptake was influenced by maternal sociodemographic factors. High vaccination uptake can be achieved in a pandemic situation. Future public health campaigns should provide clear information on vaccination safety in pregnancy, ensure consistent vaccination recommendations from healthcare professionals and provide easy access to vaccination in order to optimise uptake rates in subgroups of the population who less likely to be vaccinated. There was no association between vaccination and adverse pregnancy outcomes.

Delivery outcomes for nulliparous women at the extremes of maternal age – a cohort study

To examine the associations between extremes of maternal age (≤17 years or ≥40 years) and delivery outcomes.

Behavioural change in relation to alcohol exposure in early pregnancy and impact on perinatal outcomes - a prospective cohort study.

BackgroundThere has been limited research addressing whether behavioural change in relation to alcohol exposure in pregnancy results in better perinatal outcomes.MethodsA cohort study of 6725 women who booked for antenatal care and delivered in a large urban teaching hospital in 2010–2011. A detailed history of alcohol consumption pre-pregnancy and during early pregnancy was recorded at the first antenatal visit with follow-up of the mother and infant until discharge following birth. Adverse perinatal outcomes were compared for ‘non-drinkers’, ‘ex-drinkers’ and ‘current drinkers’.ResultsOf the 6017 (90%) women who reported alcohol consumption prior to pregnancy 3325 (55%) engaged in binge drinking and 266 (4.4%) consumed more than 14 units on average per week. At the time of booking 5649 (94%) women were ex-drinkers and of the 368 women who continued to drink 338 (92%) had a low intake (0–5 units per week), 30 (8%) an excess intake (6-20+ units per week) and 93 (25%) reported at least one episode of binge drinking. Factors associated with continuing to drink in early pregnancy included older maternal age (30–39 years), (OR 1.6; 95% CI 1.3 to 1.8), Irish nationality (OR 3.1; 95% CI 2.2 to 4.3) and smoking (OR 2.6; 95% CI 1.9 to 3.5). Ex-drinkers had similar perinatal outcomes to non-drinkers. Compared to non-drinkers current drinking was associated with an increased risk of intrauterine growth restriction (IUGR) (13% versus 19%, crude OR 1.6; 95% CI 1.1 to 2.2, adjusted OR 1.2; 95% CI 0.8 to 1.8). The greatest risk of IUGR was among women who continued to both drink and smoke, (9% versus 32%, crude OR 4.8; 95% CI 3.3 to 7.0, adjusted OR 4.5; 95% CI 3.1 to 6.7).ConclusionsPublic Health campaigns need to emphasise the potential health gains of abstaining from both alcohol and smoking in pregnancy.

Methadone dosing and prescribed medication use in a prospective cohort of opioid‐dependent pregnant women

AIMS This study aimed to (i) describe methadone dosing before, during and after pregnancy, (ii) to compare the incidence of neonatal abstinence syndrome (NAS) between those with dose decreases and those with steady or increasing doses and (iii) to describe prescribed medication use among opioid-dependent pregnant women. DESIGN Prospective cohort study. SETTING Two Irish tertiary care maternity hospitals. PARTICIPANTS A total of 117 pregnant women on methadone maintenance treatment (MMT) recruited between July 2009 and July 2010. MEASUREMENTS Electronic dispensing records from addiction clinics and the Primary Care Reimbursement Service were used to determine methadone doses and dispensed medications in the year preceding and the month following delivery. The Finnegan score was used to determine need for medical treatment of NAS. FINDINGS Of the 117 participants, sufficient dosing data were available for 89 women treated with MMT throughout pregnancy; 36 (40.4%) had their dose decreased from a mean pre-pregnancy dose of 73.3 mg [standard deviation (SD) 25.5] to a third-trimester dose of 58.0 mg (SD 26.0). The corresponding figures for those with increased doses (n = 31, 34.8%) were 70.7 mg (SD 25.3) and 89.7 mg (SD 21.0), respectively. The incidence of medically treated NAS did not differ between dosage groups. Antidepressants were dispensed for 29 women (25.7%) during pregnancy, with the rate decreasing from pre-pregnancy to postpartum. Benzodiazepines were prescribed for 43 women (38.0%). CONCLUSION In the Irish health service, opioid-dependent women frequently have their methadone dose decreased during pregnancy but this does not appear to affect the incidence of the neonatal abstinence syndrome in their babies.