On-line version ISSN 2078-5135
SAMJ, S. Afr. med. j. vol.100 n.12 Cape Town Dec. 2010
The role of prenatal alcohol exposure in abruptio placentae
M M du ToitI; M SmithI; H J OdendaalII
IMB ChB, MMed, FCOG. Department of Obstetrics and Gynaecology, Tygerberg Academic Hospital, Tygerberg, W Cape
IIMB ChB, FCOG (SA), FRCOG, MD. Department of Obstetrics and Gynaecology, Tygerberg Academic Hospital, Tygerberg, W Cape
OBJECTIVES: To investigate the association between preconception and prenatal alcohol use and abruptio placentae.
METHODS: A case-control study of women with the clinical diagnosis of abruptio placentae, 65 cases and 66 controls, at Tygerberg Academic Hospital, Western Cape, South Africa. Women in whom a retroplacental blood clot, covering at least 15% of the placental surface, was found at delivery at 24 weeks' gestation or later were asked to complete a timeline follow-back questionnaire to determine their alcohol intake 12 and 3 months before and during pregnancy. The same questionnaire was administered to a control group of high-risk women who had no antepartum haemorrhage.
OUTCOME: Women who drank alcohol 12 months before conception were more than 4 times more likely to develop abruptio placentae than the control group (odds ratio (OR) 4.49, p=0.00009). Women who drank alcohol 3 months prior to conception were 3 times more likely to develop abruptio placentae than the control group (OR 3.06, p=0.003). Drinking alcoholic beverages during pregnancy carried a more than 3 times greater risk of developing abruptio placentae (OR 3.52, p=0.0006). In the study group, women consumed a mean of 13.6, 12.0 and 11.2 standard drinks in a typical week at 12 and 3 months before and during pregnancy, respectively. The study group demonstrated a binge-drinking pattern, with two to four sessions per month.
CONCLUSION: An association was found between preconception and prenatal consumption of alcohol and abruptio placentae.
Abruptio placentae is the most common cause of stillbirth in South Africa.1 At Tygerberg Academic Hospital (TBH), a tertiary referral hospital in Cape Town, perinatal mortality data from July 2006 to June 2007 demonstrated that placental abruption was the direct cause of 25.5% of perinatal deaths where the birth weight was 1 000 g or more (unpublished data, Department of Obstetrics and Gynaecology, TBH). Although abruptio placentae is associated with many risk factors, such as cigarette smoking, growth restriction, hypertension and pre-eclampsia,2,3 a local study showed that 60% of 70 multigravidas who had had intrauterine deaths due to placental abruption had unremarkable previous obstetric histories.4 A high prevalence of cigarette smoking5 and consumption of alcohol during pregnancy6 have been noted in the coloured population, in which abruptio placentae is the main cause of stillbirth.
The question therefore arises whether there is an association between excessive exposure to alcohol before conception and during pregnancy and the development of placental abruption. Although epidemiological studies have reported increased rates of abruptio placentae in heavy drinkers during pregnancy,7-10 this association has not been investigated prospectively.
Material and methods
After approval by the Committee for Human Research of Stellenbosch University, this case-control study was performed between April 2006 and January 2008 to investigate the association between alcohol use during pregnancy and abruptio placentae. All possible cases of placental abruption were identified by the registrars on call in the labour ward by listing the women's names in the registrar's meeting room. Care was taken to include all cases of abruption, and not only the severe ones. One of the first two authors then verified the information on the woman's hospital chart to ensure that the inclusion criteria (a retroplacental blood clot covering >15% of the placental surface, gestational age >24 weeks, coloured population and singleton pregnancy) and exclusion criteria (multiple pregnancy, other causes of antepartum haemorrhage and poor knowledge of Afrikaans or English, the languages in which the interviews were conducted) were applied.
Once the woman was stable in the postnatal ward, one of the first two authors explained the study to her and obtained written informed consent for participation. Care was taken to explain that the study questionnaire did not imply that lifestyle factors were possibly responsible for the placental abruption. The timeline followback approach11 was used to obtain detailed information about daily alcohol use during a typical week a year before pregnancy, 3 months before pregnancy and during pregnancy. The amount of alcohol consumed was accurately quantified by establishing the volume and type of drink, and among how many people these drinks were shared. Illustrations of containers, bottles and glasses were used to help women to identify the specific drink and the volume consumed. For example, if a participant shared 750 ml Amarula liqueur with two drinking partners (250 ml per person, alcohol content 17%), the alcohol used per person was 34 g (250×17/100×0.8, the specific gravity (SG) of alcohol) as well as 2 000 ml wine between the three of them (666.6 ml per person, alcohol concentration 10%), the alcohol used per person was 53.3 g (666.6×10/100×0.8), giving a total of 87.3 g of absolute alcohol. For quantification of alcohol intake, a standard drink was defined as 10 g of absolute alcohol.12 Sections of the alcohol use disorder identification test (AUDIT) were used to assess the complications of heavy drinking.13
Additional information included marital status, level of formal education, preferred language, age at which first exposed to alcohol, presenting complaints, and details of previous deliveries (gestational ages, methods of delivery, birth weights and Apgar scores). For each study group case, a control case was selected at random from the postnatal wards in which the study patients were lying, applying the same inclusion and exclusion criteria. Control cases with placental abruption were not accepted, but other cases were selected from the same ward.
TBH is a tertiary referral hospital and therefore receives complicated cases only, as minor problems are managed by surrounding district hospitals. Both the study and the control groups were therefore selected from complicated obstetric referrals.
For statistical analysis STATA Statistics and Data Analysis Version 10.0, Special Edition, was used. The number and percentage of qualitative variables and the mean and standard deviation (SD) of quantitative data were calculated. Comparisons between the mean values of quantitative variables were calculated using Student's t-test, while the chi-square test was used for qualitative data. A 95% confidence interval (CI) was calculated where applicable. All tests of significance used were at the 5% level of significance.
Initially there were 66 women in both the study and the control groups, but a case was excluded from the study group because the gestational age was just below 24 weeks. Five women in the study group had a history of an abruption in a previous pregnancy, in contrast to one in the control group. Mean parity and gravidity did not differ significantly. Study cases delivered significantly earlier than control cases. Ultrasound was most commonly used to determine the gestational age (Table I). Significantly more participants (76.9%) in the study group were not married compared with the control group (54.5%). Cigarette smoking during pregnancy was reported in 72.3% of the study group and 57.6% of the control group (p=0.0785) (Table I).
In the study group, the most common presenting symptoms were antepartum haemorrhage/abdominal tenderness. In the control group, preterm labour was the most common indication for admission. The frequency of operative deliveries did not differ between the two groups, but birth weights and 5-minute Apgar scores were significantly lower in the study group (Table II). Forty per cent of the study group (26 women) reported alcohol-related problems compared with 5% (2) in the control group (p<0.0001).
Fifty-two women (80%) in the study group reported alcohol use 12 months before pregnancy. In the control group, 31 women (47%) reported the same use (OR 4.49; 95% CI 1.95 -10-62; p=0.00009). Alcohol use 3 months before pregnancy was reported by 49 women (75%) in the study group, but by 33 women (50%) in the control group (OR 3.06; 95% CI 1.458 - 6.435; p=0.003). Alcohol use during pregnancy was reported by 37 women (57%) in the study group and 18 (27%) in the control group (OR 3.52; 95% CI 1.16 -7.85; p=0.0006). Twelve (18%) women in the study group never consumed alcohol, in comparison with 28 (42%) in the control group (OR 3.25; 95% CI 1.39 - 7.8; p=0.003). Table III lists the amount and frequency of drinking in the study and control groups before and during pregnancy. The number of standard drinks taken during a typical week by women in the study group was almost double that of the control group.
Twenty-two women (34%) in the study group had pre-eclampsia, in contrast to 11 (17%) in the control group (OR 2.56; 95% CI 1.04 6.36; p=0.02). In the study group, 47 (72%) smoked cigarettes in contrast to 38 (58%) in the control group (OR 1.92; 95% CI 0.87 -4.82; p=0.08).
Women who had drunk more alcohol 12 months before, 3 months before and during pregnancy had a higher risk of developing abruptio placentae than women who did not use alcohol. Alcohol consumption was also significantly higher in the abruption group than in the control group, ranging from 112 to 136 g per week. Although this could be regarded as moderate drinking, defined as 70 -140 g of alcohol per week,14 most women had a pattern of binge drinking.
It is not clear by what mechanism exposure to heavy alcohol consumption could cause abruptio placentae. However, it is likely that placentation in early pregnancy is affected.15 In addition, poor placental function, reflected by low levels of pregnancy-associated plasma protein A in the first trimester, was associated with more stillbirths, some of which were unexplained and others caused by placental abruption.16 Furthermore, many stillbirths, including unexplained ones, are related to poor placental function.17 It is likely that folate deficiency also plays a role, as heavy drinking has an adverse effect on folate mechanism.18,19 It is therefore possible that certain cases of placental abruption are associated with folate deficiency. It is interesting to note that infants with fetal alcohol spectrum disorders have more atrial and ventricular septal defects than normal controls.20 In addition, the prevalence of these cardiac defects is higher in infants where the pregnancy was complicated by placental abruption.21 It is therefore possible that the development of both the heart and the placenta may be affected by alcohol exposure in early pregnancy. A meta-analysis has shown that the preconception administration of folic acid-containing multivitamins reduced the frequency of many congenital abnormalities, including cardiovascular defects.22 It is possible that some of these prevented defects could have been alcohol-related. Another possible mechanism is oxidative stress caused by exposure to alcohol.23,24
The higher frequency of pre-eclampsia in the control group is surprising, but it may due to selection of preterm labour for the control group. Preterm delivery is common in pre-eclampsia.25 No reports could be found on whether an association exists between heavy drinking in early pregnancy and the later development of pre-eclampsia. Our finding that cigarette smoking did not differ between the two groups was surprising, as smoking is a known risk factor for placental abruption.2,26 However, this was a small series and both groups had a high prevalence of cigarette smoking, with a trend towards more smoking in the abruption group. It is also possible that some of the known adverse effects of cigarette smoking may indeed be due to drinking, as most heavy drinkers also smoke cigarettes (Tygerberg Hospital, unpublished data), and many studies on cigarette smoking did not include drinking as a variable.
The fact that there were 32 intra-uterine deaths in the study group but no deaths in the control group demonstrates the high fetal mortality associated with placental abruption. Unfortunately no autopsies were done and no placentas sent for histological examination, as little is known about the effects of heavy drinking on the human placenta.15 Financial constraints at hospitals in developing countries limit the use of non-essential special investigations.
Limitations of this study include the introduction of selection bias, since the control group was also selected from women referred to a tertiary hospital, as reflected by their high frequency of preterm labour and caesarean section. As exposure to alcohol during pregnancy is also a risk factor for preterm labour,27 selection of the control group from a low-risk population could have resulted in a greater difference in alcohol consumption between the study and control groups. A further study defect is that no information was obtained on maternal nutrition, as this could have played a role in the poor development of placenta or abruption in some cases. Further studies are needed to confirm the association between drinking alcohol during pregnancy and abruption, in order to determine what the mechanism is and whether the prevalence of abruption could be reduced by drinking cessation programmes.
We wish to thank Dr G A Petro for his help with the statistical analyses.
Disclosure of interests. The authors are not aware of any interests to be disclosed.
Contribution to authorship. The first two authors conducted all the research relating to the questionnaires, entered the data and prepared the manuscript. The last author helped with the planning of the study, analyses and finalising the manuscript.
Details of ethics approval. The study was approved by the Committee for Human Research of Stellenbosch University. Written informed consent for the study was obtained and strict confidentiality was maintained.
Funding. No funding was needed, as the study formed part of two master's degree dissertations.
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Accepted 22 July 2010.
Corresponding author: H J Odendaal (firstname.lastname@example.org)