The Effect of Maternal Alcohol Consumption on Fetal Growth and Preterm Birth

DOI: 10.1111/j.1471-0528.2008.02058.x Epidemiology www.blackwellpublishing.com/bjog

The effect of maternal alcohol consumption on fetal growth and preterm birth

CM O’Leary,a N Nassar,a JJ Kurinczuk,b C Bowera a Division of Population Sciences, Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, WA, Australia b National Perinatal Epidemiology Unit, University of Oxford, Headington, Oxford, UK Correspondence: Ms CM O’Leary, Division of Population Sciences, Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, PO Box 855, West Perth, WA 6872, Australia. Email [email protected]

Accepted 26 October 2008.

Objective To investigate the relationship between prenatal alcohol association between alcohol intake and SGA infants was exposure and fetal growth and preterm birth and to estimate the attenuated after adjustment for maternal smoking. Low levels of effect of dose and timing of alcohol exposure in pregnancy. prenatal alcohol were not associated with preterm birth; however, binge drinking resulted in a nonsignificant increase in odds. Design A population-based cohort study linked to birth Preterm birth was associated with moderate and higher levels of information on the Western Australian Midwives Notification prenatal alcohol consumption for the group of women who System. ceased drinking before the second trimester. This group of Setting Western Australia. women was significantly more likely to deliver a preterm infant than women who abstained from alcohol (adjusted OR 1.73 [95% Population A 10% random sample of births restricted to CI 1.01–3.14]). nonindigenous women who had delivered a singleton infant (n = 4719) in 1995–1997. Conclusions Alcohol intake at higher levels, particularly heavy and binge drinking patterns, is associated with increased risk Methods The impact of alcohol consumption in pregnancy on of preterm birth even when drinking is ceased before the fetal growth (small-for-gestational-age [SGA] and large-for- second trimester. This finding, however, is based on small gestational-age infants [LGA]) and preterm birth (<37 weeks of numbers and needs further investigation. Dose and timing of gestation) was assessed using multivariate logistic regression prenatal alcohol exposure appears to affect preterm delivery analysis and adjusting for confounding factors. andshouldbeconsideredinfutureresearchandhealth Main outcome measures Odds ratios and 95% CI, attributable education. risk, and population attributable risk were calculated. Keywords Fetal growth, high risk, pregnancy, prenatal alcohol Results The percentage of SGA infants and preterm birth increased exposure, preterm birth, RASCALS, small for gestational age. with higher levels of prenatal alcohol exposure; however, the

Please cite this paper as: O’Leary C, Nassar N, Kurinczuk J, Bower C. Impact of maternal alcohol consumption on fetal growth and preterm birth. BJOG 2009;116:390–400.

Introduction tions, which prevented their results from being generalised to the wider community. The evidence surrounding the effect of low to moderate In the few studies that have reported an association intake of alcohol during pregnancy on fetal growth and pre- between low levels of prenatal alcohol exposure and fetal term birth is inconclusive. While there is a large body of growth, the direction of the association has not been consis- literature on the issue, the evidence base has many weaknesses tent. While the majority of studies have reported no associa- limiting our ability to reach deﬁnitive conclusions. In their tion with less than 72 g of alcohol per week (equivalent to systematic review of the literature, Henderson et al. (2007)1 seven standard drinks per week in Australia; six in the reported that many studies did not control for known con- USA, Canada, and Europe; and nine units in the UK) and founding factors, such as cigarette smoking and ethnicity. In low birthweight,3–9 intrauterine growth restriction,5,10,11 and their more detailed report,2 the authors found that the studies preterm birth,8,10,12–17 a small number of studies found an that had adjusted for confounding factors had other limita- increased risk at low levels18–20 and, conversely, others have

390 ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology The effect of prenatal alcohol on fetal outcomes reported a possible protective effect of low levels of alcohol or never) and the quantity consumed (e.g. number of cans, consumption in pregnancy.10,13,18,21–23 At higher levels of pre- glasses, bottles) on a typical occasion for each of four types of natal alcohol exposure, the findings of an association between alcoholic beverages (beer, wine/champagne, spirits/liqueurs, prenatal alcohol exposure and fetal growth are not consistent, and fortified wines). Consumption frequency calculations with around half of studies reporting no significant associa- used the lower of the days marked, for example 3–4 days/week tion3,4,10,18,24–31 and half reporting a significant associa- was included as 3 days/week to calculate total weekly dose tion.9,20,32–40 Uncertainty also exists about the impact of of alcohol. However, there were a small number of women binge drinking on intrauterine growth and questions remain (n = 7 in first trimester and n = 1 in third trimester) who as to whether the increased risk from binge drinking, if one reported a frequency of drinking of one to two times per week truly exists, is due to the pattern of binge drinking per se or and who consumed two or more types of beverages each at rather a result of heavy alcohol intake.2 less than 50 g per occasion, but with a total weekly consump- Using data from a population-based cohort study of non- tion of 70+ g. As we could not be confident that the women indigenous women in Western Australia (WA), this study had consumed only once per week, and therefore, at binge examines the impact of maternal alcohol consumption, taking levels, we coded them as heavy drinkers. Where respondents into account the quantity per occasion, frequency of con- used a tick mark instead of indicating a numeric value, a sumption, and total quantity consumed during the 3 months minimum level for the type of beverage, time period, and before and during each trimester of pregnancy on preterm frequency was applied. Standard drink calculations were birth and fetal growth. derived during the data analysis stage and covered a range of measures for each type of beverage;42 more details are avail- Materials and methods able on request from the authors. To examine the impact of the pattern of drinking by The details of the study used for this analysis have been women before and during pregnancy, we took into account described previously.41–43 Briefly, a 10% random sample of the frequency, quantity per occasion, and total quantity con- all women giving birth in WA between 1995 and 1997 was sumed. The level of alcohol consumption was categorised into invited by letter at 12 weeks postpartum to participate in five mutually exclusive groups; none, low, moderate, binge a postal survey of health-related behaviours and events during (less than weekly up to twice per week), and heavy (including pregnancy and infancy (subsequently known as the RASCALS women who binged more than twice per week) (Table 1). For study), designed to survey health-related behaviours and the analyses, abstinence during pregnancy refers to women events before and during pregnancy and early infancy. Data who reported not drinking at any stage during pregnancy. were collected using a postal questionnaire sent with the letter One standard drink in Australia is equal to 10 g of alcohol. of invitation. Mothers whose infants were stillborn (n = 20) or The ‘low’ category was defined in line with the 2001 recom- given up for adoption (n = 5) were excluded. An 81% mendation to women who are pregnant or might soon response rate resulted in 4861 completed questionnaires of become pregnant set out by the Australian National Health which 4860 were able to be linked to their corresponding and Medical Research Council alcohol guideline 11, which birth information on the WA Midwives’ Notification System, recommends that ‘If women choose to drink, over a week, a statutory population-based surveillance system of all births should have less than 7 standard drinks, AND, on any one in WA. The analysis reported here was restricted to women day, no more than 2 standard drinks’.45 To assess the overall with singleton births (multiples n = 66) and nonindigenous impact of alcohol intake greater than the low level, moderate, mothers (indigenous n = 75), giving a sample size of 4719. heavy, and binge drinking were also combined. Comparison with data available for all births in WA in this The primary outcomes of the study were the effect of alcohol period44 showed that the respondents were representative of consumption in pregnancy on fetal growth and preterm birth. mothers of all singleton live births with the exception of a slight Appropriate fetal growth was ascertained using the proportion underrepresentation of mothers with low-birthweight babies of optimal birthweight (POBW), where optimal birthweight (5.3% overall versus 4.7% respondents) and mothers aged less was determined after taking into account infant sex, gestational than 20 years (6.0% overall versus 3.6% respondents; 2.5% in this age, maternal height, and parity. The POBW was then calcu- sample). Ethics approval for the conduct of this study was granted lated by taking the ratio of observed birthweight to optimal by the Princess Margaret Hospital Research Ethics Committee birthweight.46 The population selected to define optimal birth- and the WA Confidentiality of Health Information Committee. weight was the total 1998–2002 WA population of singleton, Information about maternal alcohol consumption was col- Caucasian births, not exposed to factors known to influence lected retrospectively for the 3-month period prepregnancy fetal growth pathologically. We used a POBW score less than and for each trimester separately. For each period, women the 10th percentile to define small-for-gestational-age (SGA) were asked how often they drank alcohol (5 or more, 3–4, infants. Preterm birth was defined as infants born at less than or 1–2 days/week; 1–2 days/month; less than once per month; 37 weeks of gestation. Gestational age was estimated using an

ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology 391 O’Leary et al.

Table 1. Classiﬁcation of maternal alcohol consumption

Alcohol consumption (g)

Low Moderate* Binge

Frequency per week

Grams per occasion*** •20 20–<50 501 >10–501

Grams per week*** •60 •70 ‚5 ‚68

Prepregnancy Mean 9.3 21.5 60.3 208.7 Median 3.8 12.5 50.6 141.0 Minimum 0.5 2.1 5.0 68.0 Maximum 60.0 70.0 320.0 3685.0 Trimester 1 Mean 6.2 16.6 58.0 192.5 Median 2.5 8.0 50.0 150.0 Minimum 0.5 2.1 5.0 71.0 Maximum 60.0 67.5 270.0 1453.0 Trimester 2 Mean 6.0 14.6 48.0 161.1 Median 2.5 7.5 25.3 120.0 Minimum 0.5 2.1 5.0 75.0 Maximum 60.0 66.0 265.0 540.0 Trimester 3 Mean 6.0 15.2 47.0 143.2 Median 2.5 7.6 25.0 105.0 Minimum 0.5 3.0 5.0 74.0 Maximum 60.0 70.0 265.0 540.0

*Women reporting consuming 10 g of alcohol per occasion on a daily basis are included in the moderate group. **,Weekly 5 one to two times per month to once every 8–10 weeks. ***10 g 5 one standard drink in Australia and 50 g per occasion 5 binge drinking. algorithm taking into account two independent estimates of level of alcohol and a 70% increase in the odds for the off- gestational duration from routinely collected data (last men- spring of women consuming a moderate level of alcohol. Due strual period, expected due date, ultrasound fetometry, baby’s to the small numbers in the specific categories, there was only date of birth, and neonatal estimate of gestational age) by the limited power to detect a statistically significant difference for WA Midwives’ Notification System.47 heavier drinking levels. The effect of alcohol consumption in specific periods of The association between alcohol consumption both before pregnancy was examined by investigating infant outcomes for and during pregnancy and risk of SGA infants compared with women who only drank in the first trimester, those who drank in infants of abstinent women was assessed using logistic regres- the first trimester regardless of whether they stopped or contin- sion analysis. In addition, we used the same method to assess ued drinking later in pregnancy, and the outcomes for women the association between prenatal alcohol and large-for-gesta- who drank in either trimesters 2 and/or 3 irrespective of whether tional-age (LGA) infants, using a POBW score greater than they drank in first trimester, referred to as ‘late’ pregnancy. The the 90th percentile to define LGA infants. We also conducted maximum alcohol intake in each respective period was used to generalised linear regression analysis of POBW to ensure we assign the level of drinking and where alcohol consumption was had not missed any information by categorising the variable. missing for the third trimester (n = 27), the second trimester Cox regression was used to determine independent risk fac- alcohol consumption information was assigned. tors for preterm birth. The analyses were adjusted for poten- This study had 80% power at a 95% level of confidence to tial confounders: maternal smoking and illicit drug use detect a 50% increase in the odds of preterm birth or poor (tranquillizers, marijuana, ecstasy, amphetamines, heroin, fetal growth (OR 1.50) for infants of women consuming a low methadone, cocaine, lysergic acid diethylamide [LSD], and

392 ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology The effect of prenatal alcohol on fetal outcomes volatile substances) during pregnancy, maternal age, parity, 20% of women abstained during the prepregnancy period, this ethnicity, marital status and income (all self-reported), and increased to 57% in the first two trimesters, decreasing to 54% maternal medical conditions (essential hypertension, pre- in the third trimester. Only 41% of women abstained through- existing diabetes mellitus, asthma, and genital herpes); preg- out each trimester of pregnancy (results not shown). Approx- nancy complications (threatened miscarriage, threatened pre- imately one-third of women consumed a low level of alcohol term labour, urinary tract infection, pre-eclampsia, placenta before and during pregnancy. There was a marked reduction at praevia, abruption, antepartum haemorrhage, prelabour rup- higher levels of consumption with the percentage of women ture of membranes, and gestational diabetes); or pregnancy drinking at heavy and binge levels dropping from around 10– procedures (ultrasound, fertility treatments, cervical suture, 3% between the prepregnancy and the first trimester. chorionic villus sampling/placental biopsy, amniocentesis, There were 421 (8.9%) infants who were SGA (POBW less and antepartum and intrapartum cardiotocogram), identified than 10th percentile) and 265 (5.7%) infants were delivered from the WA Midwives’ Notification System. As self-reported before 37 weeks of gestation. Overall, there was little differ- income was missing for 17% of the cohort, the relative Index ence between the outcomes for infants of women who drank for Socio-Economic Disadvantage48 was applied as a proxy for low levels of alcohol during pregnancy and those of women missing cases. Interaction terms were tested for but were not who were abstinent during pregnancy (Table 3). The percent- included in the analysis as they did not make a statistically age of growth-restricted infants was highest among those significant (r < 0.01) contribution to the fit of the data. Data exposed to either maternal binge or heavy drinking during analyses were conducted using SPSS version 15.0, and results pregnancy, around 13% for each group. For preterm births, are presented as odds ratios with 95% CI. the percentage of infants born before 37 weeks was highest The population attributable risk (PAR) and the attributable among those exposed to binge drinking during late pregnancy risk (AR)49 for preterm birth were calculated for alcohol (9.5%) and for children born to mothers who drank heavily exposure in the group of women who stopped drinking at but stopped drinking before the second trimester (13.6%). moderate, heavy, and binge levels before second trimester. The distribution of maternal characteristics by alcohol use is shown in Table 4. The prevalence of smoking in the whole Results cohort was 24.6%, with 10.6% of women smoking >10 ciga- rettes per day. Women who reported smoking at any time dur- The quantity of alcohol consumed per week during pregnancy ing pregnancy were less likely to abstain from alcohol during is presented in Table 1. Levels of alcohol intake decreased their pregnancy and to comprise a larger percentage of the from the prepregnancy period to trimester 2 for each level women who continued to drink during late pregnancy of alcohol exposure, particularly the maximum intake for (27.7%). Predictive factors for continuing to drink during late women with a binge or heavy drinking pattern. The median pregnancy were maternal age 30 years and older, higher income, intake for women drinking at low to moderate levels other drug use, Caucasians, and married women. A higher per- decreased by approximately one-third between prepregnancy centage of women who stopped drinking before the second tri- and first trimester but did not decrease markedly in late preg- mester reported that the pregnancy had been unplanned (55%) nancy. Conversely, there was little change in the median than women who were abstinent during pregnancy (47%). intake at higher levels of intake until late pregnancy when Table 5 shows the elevated odds of SGA infants with mod- the median for binge drinkers halved and decreased by one- erate to heavy alcohol consumption in pregnancy and how, third for heavy drinkers. Around 9% of women drinking at after adjustment for smoking status, this effect is eliminated. heavy levels during prepregnancy consumed more than 400 There was, however, an increased odds of infants being born g/week (data not shown). SGA following low levels of alcohol in the prepregnancy period The distribution of maternal alcohol consumption before (adjusted OR [aOR] 1.34, 95% CI 0.99–1.82) that attained and during pregnancy is shown in Table 2. While fewer than significance in the fully adjusted generalised linear model

Table 2. Pattern of maternal alcohol consumption before and during pregnancy

Pattern of drinking Prepregnancy, n (%) Trimester 1, n (%) Trimester 2, n (%) Trimester 3, n (%)

Abstinent 919 (19.5) 2707 (57.4) 2688 (57.0) 2537 (53.8) Low 1557 (33.0) 1326 (28.1) 1542 (32.7) 1668 (35.3) Moderate 1282 (27.2) 446 (9.5) 367 (7.8) 402 (8.50) Binge two times per week 512 (10.8) 131 (2.8) 56 (1.2) 43 (1.0) Heavy 449 (9.5) 108 (2.3) 66 (1.4) 69 (1.5)

ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology 393 O’Leary et al.

Table 3. Distribution of SGA and gestational age by maternal alcohol consumption before and during pregnancy

Abstinent, n (%) Low, n (%) Moderate, n (%) Binge •two times Heavy, n (%) per week, n (%)

Drank during prepregnancy Percentage optimal birthweight 10% 844 (91.8) 1398 (89.9) 1177 (92.0) 464 (90.6) 410 (91.5) SGA ,10% 75 (8.2) 157 (10.1) 103 (8.0) 48 (9.4) 38 (8.5) Gestational age 37 weeks 865 (94.1) 1426 (93.9) 1210 (94.5) 489 (95.5) 423 (94.4) Preterm delivery ,37 weeks 54 (5.9) 93 (6.0) 70 (5.5) 23 (4.5) 25 (5.6) Drank during trimester 1 Percentage optimal birthweight 10% 1752 (91.2) 1199 (90.6) 408 (91.5) 114 (87.0) 94 (87.0) SGA ,10% 170 (8.8) 125 (9.4) 38 (8.5) 17 (13.0) 14 (13.0) Gestational age 37 weeks 1812 (94.3) 1252 (94.6) 424 (95.1) 121 (92.4) 102 (94.4) Preterm delivery ,37 weeks 110 (5.7) 72 (5.4) 22 (4.98) 10 (7.6) 6 (5.6) Alcohol consumed in trimester 1 with abstinence in late pregnancy* Percentage optimal birthweight 10% 1752 (91.2) 208 (90.0) 80 (88.9) 33 (89.2) 20 (90.9) SGA ,10% 170 (8.8) 23 (10.0) 10 (11.1) 4 (10.8) 2 (9.1) Gestational age 37 weeks 1812 (94.3) 219 (94.8) 82 (91.1) 33 (89.2) 19 (86.4) Preterm delivery ,37 weeks 110 (5.7) 12 (5.2) 8 (8.9) 4 (10.8) 3 (13.6) Drank during late pregnancy* Percentage optimal birthweight 10% 1752 (91.2) 1640 (91.3) 436 (92.4) 55 (87.3) 69 (86.3) SGA ,10% 170 (8.81) 157 (8.7) 36 (7.6) 8 (12.7) 11 (13.8) Gestational age 37 weeks 1812 (94.3) 1700 (94.6) 452 (95.8) 57 (90.5) 75 (93.8) Preterm delivery ,37 weeks 110 (5.7) 97 (5.4) 20 (4.2) 6 (9.5) 5 (6.3)

*Second and/or third trimesters.

(adjusted b –1.66, 95% CI –2.94 to –0.39) (results not ped drinking before second trimester were 11.4 and 19.4%, shown), but this association was not observed at higher lev- respectively. els of alcohol in prepregnancy or in any other analyses investigating the other time periods during pregnancy. The odds Discussion of an infant being LGA were close to or below one for all levels of alcohol exposure in each time period; however, This study has been able to investigate the effect of different none was statistically significant. levels of alcohol consumption on fetal growth and preterm There was no evidence of an increased likelihood of preterm birth taking into account the quantity per occasion, frequency birth at low levels of alcohol after adjusting for covariates of consumption, and total quantity consumed. The findings (Table 6). There was a nonsignificant increase in the odds of of our study demonstrate that low levels of alcohol consumed preterm birth with binge drinking in pregnancy, aOR 1.31 (95% during pregnancy at levels less than 60 g/week and not more CI 0.67–2.58) in first trimester and aOR 1.61 (95% CI 0.68– than two standard drinks per occasion were not associated 3.77) in late pregnancy, although the results lack precision due with preterm birth or SGA infants. Moderate to heavy alcohol to small numbers. Combining all women who drank at greater intake resulted in an increased risk of preterm birth only in than low levels during late pregnancy resulted in a masking of women who stopped drinking before the second trimester. the association at higher levels, aOR 0.90 (95% CI 0.60–1.37). There was no association between alcohol consumption dur- Women with a heavy pattern of alcohol intake in the first ing pregnancy and SGA infants after taking into account trimester and who stopped drinking by the second trimester smoking status. had a nonsignificant, two-fold increased odds of preterm Our results highlight an increasing trend in the risk of birth (aOR 2.30, 95% CI 0.69–7.72). There was a trend for preterm birth with increasing levels of alcohol exposure, moderate or higher levels of alcohol to increase the odds of although findings were imprecise due to small numbers. Many preterm birth. Analysis combining moderate and higher levels previous studies have not differentiated the pattern of alcohol of alcohol consumption yielded a 78% increased odds of pre- consumption. By combining infrequent and weekly binge term birth (aOR 1.78, 95% CI 1.01–3.14). drinking with drinking at low levels (an average of less than The PAR and AR for preterm birth for combined moderate, one drink per day), the association was (likely to be) masked.1,40 heavy, and binge exposure in the group of women who stop- The tendency for researchers to group together all women

394 ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology The effect of prenatal alcohol on fetal outcomes

Table 4. Maternal characteristics by alcohol consumption before and during pregnancy

Alcohol consumption

Whole Cohort Prepregnancy During pregnancy (%), n 5 4719 Abstinent Abstinent Drank Stopped before Drank during late* (%), (%), trimester 1 (%), trimester 2 (%), pregnancy (%), n 5 919 n 5 1924 n 5 2011 n 5 380 n 5 2415

Maternal age group (n 5 4717) ,20 2.5 2.4 34.4 2.3 3.4 1.8 20–24 14.4 17.0 3.2 30.4 22.1 11.5 25–29 32.3 34.8 16.6 13.2 30.9 30.6 30–44 50.8 45.8 45.9 54.1 43.6 56.0 Smoking** (n 5 4688) None 74.7 83.3 81.0 67.6 64.6 71.8 10 per day 14 8.0 10.4 18.4 17.7 16.6 .10 per day 10.6 8.8 8.6 14.0 17.7 11.1 Ethnic group (n 5 4714) Caucasian 92.8 78.6 86.6 96.7 96.3 97.4 Other 7.1 21.4 13.4 3.3 3.7 2.6 Marital status (n 5 4700) Married 75.9 81.0 77.4 72.5 60.6 77.3 Defacto 17.5 13.4 16.4 20.4 25.6 17.2 Single 6.2 5.6 6.2 7.1 13.4 5.1 Parity (n 5 4714) First 29.1 24.6 29.5 29.8 37.2 27.5 Second 31.2 30.3 30.2 30.9 30.3 32.3 Third1 39.6 45.2 40.3 39.3 32.4 40.2 Drug use during pregnancy (n 5 4719) No 92.9 95.9 95.8 90.0 91.8 90.8 Yes 7.1 4.1 4.2 10.0 8.2 9.2 Income (n 5 4666) Most advantaged .$40 000 28.5 19.9 22.8 32.4 23.4 34 $25 001–40 000 30.8 39.5 39.9 38.4 41.5 39.3 Most disadvantaged $25 001 39.6 39.5 36.2 28.2 34.0 25.7 Maternal medical conditions (n 5 4717) None 81.3 80.8 80.9 82.3 80.3 81.8 Any 18.7 19.2 19.1 17.7 19.7 18.2 Procedures and treatments during pregnancy (n 5 4717) None 7.5 6.2 7.1 7.5 5.1 8.2 Ultrasound 57.2 57.6 58.1 35.5 58.5 56.2 Other 35.4 36.2 34.9 57.0 36.4 35.6 Pregnancy complications (n 5 4719) None 72.3 71.1 71.8 73.1 69.4 73.1 One or more 27.7 28.9 28.2 29.0 30.6 26.9 Unplanned pregnancy (n 5 4395) No 46.9 46.2 47.1 43.8 38.3 41.2 Yes 46.2 47.4 47.2 49.7 55.3 38.6

*Second and/or third trimesters. Note that numbers may vary due to missing covariate data. **Smoking at any stage during pregnancy. consuming an average of one drink or more per day also appears icantly increased when consumption at moderate and higher to conceal the association between dose and outcome. levels was combined. These results are similar to those The potential risk of preterm birth for women who ceased reported by Jaddoe et al.40 who found an adjusted 2.5-fold alcohol consumption before the second trimester was signif- increase in the risk of preterm birth with an average of one or

ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology 395 O’Leary et al.

Table 5. OR (and 95% CI) for the association between alcohol consumption categories before and during pregnancy and SGA (POBW <10%)

Alcohol consumption and timing of exposure Frequency Unadjusted Adjusted for smoking Fully adjusted*

n SGA OR 95% CI OR 95% CI OR 95% CI

Prepregnancy Abstinent 919 75 Referent 1.0 Low 1557 157 1.27 0.95–1.69 1.24 0.92–1.66 1.34 0.99–1.82 Moderate 1282 103 0.99 0.72–1.34 0.96 0.70–1.32 1.05 0.75–1.46 Binge occasional 512 48 1.16 0.80–1.70 0.82 0.55–1.22 0.93 0.62–1.40 Heavy 449 38 1.04 0.69–1.57 0.81 0.53–1.24 0.83 0.53–1.30 Alcohol consumption during trimester 1 Abstinent 1924 170 Referent 1.0 Low 1326 125 1.07 0.84–1.36 1.05 0.82–1.35 1.08 0.84–1.40 Moderate 446 38 0.96 0.67–1.38 0.85 0.58–1.23 0.87 0.59–1.29 Binge occasional 131 17 1.54 0.90–2.62 0.91 0.52–1.59 0.98 0.55–1.71 Heavy 108 14 1.54 0.86–2.75 0.84 0.44–1.59 0.82 0.42–1.59 Alcohol consumed in trimester 1 with abstinence in late pregnancy Abstinent 1924 170 Referent 1.0 Low 231 23 1.14 0.72–1.80 1.06 0.66–1.68 1.09 0.68–1.75 Moderate 90 10 1.29 0.66–2.53 1.11 0.56–2.20 1.10 0.55–2.21 Binge occasional 37 4 1.25 0.44–3.57 0.83 0.29–2.43 0.91 0.31–2.72 Heavy 22 2 1.03 0.24–4.45 0.75 0.17–3.31 0.72 0.16–3.26 Maximum consumption during late pregnancy** Abstinent 1924 170 Referent 1.0 Low 1800 157 0.98 0.79–1.24 0.96 0.76–1.21 1.00 0.78–1.28 Moderate 472 36 0.85 0.59–1.24 0.75 0.51–1.10 0.79 0.53–1.17 Binge occasional 63 8 1.50 0.70–3.20 0.86 0.40–1.88 0.86 0.39–1.92 Heavy 80 11 1.64 0.85–3.17 1.04 0.51–2.09 1.03 0.50–2.10

*Adjusted for maternal age, smoking, ethnicity, marital status, parity, drug use, income, maternal medical conditions, procedures, and treatments during pregnancy and pregnancy complications. **Second and/or third trimesters. Note that numbers may not add up to the total due to women who abstained in First Trimester but drank in Late Pregnancy (n5784, 17%) and those who abstained in Late Pregnancy but drank in First Trimester (n5380, 8%). more drinks of alcohol per day until pregnancy recognition. 1 error cannot be ruled out. It is, however, an issue warranting There are several possible explanations for the greater risk of further investigation as our results indicate that, if this is a true adverse infant outcomes among women who ceased drinking finding, around 11% of preterm births would be attributable before the second trimester that we have not been able to to this pattern of drinking. Prevention of high-risk drinking investigate in this study. Although we adjusted for maternal in early pregnancy could potentially minimise preterm birth medical complications in general, there may be specific health and associated adverse developmental outcomes for the child problems for which women stop consuming alcohol and that and reduce costs on the healthcare system. predispose them to preterm birth that we were unable to Our study highlights that fetal growth appears to be much investigate. Another potential reason may be that cessation more influenced by the effects of smoking than alcohol. The of alcohol consumption before second trimester may trigger negative association between low levels of alcohol in prepreg- an inflammatory or other metabolic response resulting in nancy and SGA infants was not observed with higher levels of elevation of inflammatory cytokines and thereby increasing exposure in prepregnancy. This association is likely to reflect the risk of preterm birth.50,51 Furthermore, it is possible that the influence of unmeasured confounding factors rather than some or all the women reporting cessation actually continued a true association. Our results are consistent with the majority to drink during late pregnancy, although given the lack of of studies investigating low to moderate prenatal alcohol dose response observed in late pregnancy, this is unlikely to exposure and the power of our study to detect a difference explain our findings. at these levels was reasonable. While our study is in agreement It should be noted that the finding of increased odds of with half of the studies examining higher levels of prenatal preterm delivery in women ceasing alcohol consumption alcohol exposure, the lack of power in our study at higher before second trimester is based on small numbers and a type levels of prenatal alcohol exposure precludes firm conclusions

396 ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology The effect of prenatal alcohol on fetal outcomes

Table 6. OR (and 95% CI) for the association between alcohol consumption categories before and during pregnancy and preterm birth (<37 weeks)

Alcohol consumption and timing of exposure Frequency Unadjusted Adjusted for smoking Fully adjusted*

n Preterm birth OR 95% CI OR 95% CI OR 95% CI

Prepregnancy Abstinent 919 54 Referent 1.0 Low 1557 93 0.89 0.73–1.43 1.00 0.72–1.41 1.13 0.79–1.59 Moderate 1282 70 0.71 0.66–1.33 0.94 0.66–1.35 1.05 0.72–1.52 Binge two times per week 512 23 0.77 0.47–1.25 0.75 0.46–1.23 0.83 0.50–1.38 Heavy 449 25 0.83 0.59–1.53 0.94 0.58–1.51 1.05 0.64–1.74 Alcohol consumption during trimester 1 Abstinent 1924 110 Referent 1.0 Low 1326 72 0.95 0.71–1.28 0.96 0.71–1.30 1.04 0.76–1.41 Moderate 446 22 0.86 0.55–1.37 0.90 0.56–1.42 0.93 0.58–1.49 Binge two times per week 131 10 1.31 0.69–2.51 1.27 0.65–2.49 1.31 0.67–2.58 Heavy 108 3 0.97 0.43–2.21 0.93 0.40–2.13 1.09 0.46–2.54 Alcohol consumed in trimester 1 with abstinence in late pregnancy Abstinent 1924 110 Referent 1.0 Low 231 12 0.91 0.50–1.65 0.91 0.50–1.65 0.91 0.49–1.66 Moderate 90 8 1.59 0.78–3.26 1.60 0.78–3.29 1.67 0.80–3.46 Binge two times per week 37 4 1.89 0.70–5.11 1.73 0.63–4.79 1.65 0.58–4.69 Heavy* 22 3 2.59 0.82–8.15 2.26 0.71–7.23 2.30 0.69–7.72 .Low combined 149 15 1.81 1.05–3.10 1.73 1.00–3.00 1.78 1.01–3.14 Maximum consumption during late pregnancy** Abstinent 1924 110 Referent 1.0 Low 1800 97 0.94 0.72–1.24 0.95 0.72–1.24 0.99 0.75–1.32 Moderate 472 20 0.74 0.46–1.19 0.75 0.47–1.21 0.77 0.48–1.26 Binge two times per week 80 6 1.65 0.72–3.75 1.52 0.66–3.51 1.61 0.68–3.77 Heavy 63 5 1.08 0.44–2.64 1.03 0.42–2.55 1.09 0.44–2.72 .Low combined 615 30 0.88 0.59–1.24 0.87 0.58–1.30 0.90 0.60–1.37

*Adjusted for maternal age, smoking, ethnicity, marital status, parity, drug use, income, maternal medical conditions, procedures, and treatments during pregnancy and pregnancy complications. **Second and/or third trimesters. Note that numbers may not add up to the total due to women who abstained in First Trimester but drank in Late Pregnancy (n=784, 17%) and those who abstained in Late Pregnancy but drank in First Trimester (n=380, 8%). from being made for very heavy alcohol consumption. A allowed us to address some of the main limitations identified significantly increased risk for women drinking an average in the recent systematic review by Henderson et al.,1 specifi- of three or more drinks per day across pregnancy has been cally, to examine the impact of low levels of alcohol consump- reported by one study.39 The relatively small numbers of tion during pregnancy with sufficient power to detect a 50% women drinking at these levels in our study, particularly in increase in the odds of an effect for women drinking at low to late pregnancy, limited our ability to look at this group sep- moderate levels. arately, so we cannot rule out that a higher risk is associated Underreporting of alcohol consumption is always a poten- with this level of exposure. tial concern to epidemiological studies and although we can- The key strengths of this study are that it includes a ran- not confirm if underreporting occurred in this study, there domly selected population-based cohort with a high response are a number of factors that we believe would have limited rate, thereby enabling the results to be generalised to the wider underreporting. In Australia, alcohol consumption during population, and we were able to adjust for a comprehensive pregnancy is very prevalent with almost 50% of women in range of known confounding factors including maternal our study consuming alcohol during pregnancy; this percent- behaviours and socio-demographic factors. While there may age is similar to earlier Australian studies.52 Screening for have been factors associated with heavy drinking that we were alcohol use during pregnancy and information on the risks not able to account for, adjustment for known confounders from prenatal alcohol exposure are not routinely undertaken such as smoking and socio-economic status is likely to have by WA health professionals53 and there were no public health accounted, at least in part, for their effect. Our results have campaigns on this issue either before or during the study.

ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology 397 O’Leary et al.

Reporting of prenatal alcohol consumption is influenced Contribution to authorship by the method and the timing of the questions.54–59 In this J.J.K. designed, obtained funding, and ran the original cohort study study, information on alcohol consumption during preg- from which these data arose. Ms C.M.O. was the primary contributor nancy was collected after the outcome of pregnancy was to the paper in relation to the concept and design, analysis and known so it is possible that recall bias may have occurred in interpretation of the results, and drafting of the article. N.N. and some instances. Our data, however, were collected by self- C.B. supervised Ms C.M.O. in the analysis of the data. All authors contributed to the interpretation of results, reviewing the article and administered questionnaire, which has been shown to elicit provided final approval for the version to be published. more valid responses on socially sensitive issues and reveal 56 more unwanted behaviour than interviews. Studies have Ethics approvals indicated that misclassification of prenatal alcohol consump- Ethics approval for the conduct of this study was granted by the 54,58–60 tion collected retrospectively is rare and thus is unlikely Princess Margaret Hospital Research Ethics Committee and the 58,60 to have had a profound influence on our findings, WA Confidentiality of Health Information Committee. although we accept this remains a possibility. Although self-administered questionnaires have been Funding reported to underestimate prenatal binge drinking,55 estima- The Western Australian survey of health-related behaviours and tion of binge drinking in our survey was not obtained through events during pregnancy and early infancy was funded by a grant a specific question on binge drinking. Instead, it was calcu- from Healthway (the Western Australian Health Promotion Foun- lated from responses to questions on frequency, quantity con- dation 8016). J.J.K. was partially funded by a National Public Health sumed type of beverage, and measure (e.g. cans, glasses), Career Scientist award from the Department of Health and National which were asked together with questions on a range of pre- Health Services Research and Development (PHCS022) when this natal maternal behaviours and family factors, so the focus of analysis was conducted. This study was supported by the Australian National Health and Medical Research Council (NHMRC) program the survey was not exclusively upon alcohol consumption. grant numbers 353514 (2005–2009), NHMRC Research Fellowship However, if alcohol intake was underestimated in our study, (353628) (C.B.) and NHMRC Public Health (Australia) Fellowship the bias would likely be towards the null. (404118) (N.N.). The trend to increased risk of preterm birth when mothers binge or drink heavily during pregnancy, even occasionally, Acknowledgements highlights the importance of screening all women of child- The authors thank Margaret Wood, Peter Cosgrove, and Vivien Gee bearing age for alcohol use and promoting abstinence or less for maintenance of the databases. j risky patterns of drinking. The increasing tendency for young women in general to drink at risky levels, including binge drinking,61,62 should be recognised as an important modifi- References able cause of preterm birth and efforts need to be made to 1 Henderson J, Gray R, Brocklehurst P. Systematic review of effects of reverse this trend especially before women conceive. low-moderate prenatal alcohol exposure on pregnancy outcome. BJOG 2007;114:243–52. 2 Gray R, Henderson J. Review of the Fetal Effects of Prenatal Alcohol Conclusions Exposure. Oxford, UK: National Perinatal Epidemiology Unit, University Our results highlight the importance of taking into account the of Oxford, 2006. 3 Shu XO, Hatch MC, Mills JJ, Clemens JJ, Susser MM. Maternal smok- pattern of maternal drinking when estimating risk. This pop- ing, alcohol drinking, caffeine consumption, and fetal growth: results ulation-based cohort study showed no evidence of an associa- from a prospective study. 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