2.3.1 The effects of alcohol on reproduction and pregnancy
One of the damaging effects alcohol can have in relation to reproductive health is on sexual dysfunction and infertility. In both men and women, there is a link between alcohol and sexual dysfunction (Peugh & Belenko, 2001), although the level at which the risk of reproductive function is affected is unclear (Sharma et al., 2013). Evidence suggests that higher levels of alcohol consumption decrease the chances of conceiving, as involuntary childlessness is more prevalent among women who report drinking at high levels (Eggert, Theobald & Engfeldt, 2004; Rostad, Schei & Sundby, 2006; Tolstrup et al., 2003). For example, Tolstrup et al. (2003) found that women aged 30 years or older who drank seven or more drinks (one drink equals 12g of pure alcohol) per week had an increased risk of infertility compared to women who drank less than one drink per week (hazard ratio (HR) = 2.26, 95% CI: 1.19–4.42). While reproductive function is not the focus of this research, primary prevention of high levels of alcohol consumption in the pre-pregnancy period could also have an impact on infertility.
During pregnancy, alcohol also increases the risk of negative neonatal outcomes. Increased risk of low birth weight (LBW) (Brooke et al., 1989; Valero De Bernabé et al., 2004), small for gestational age (SGA) (Chiaffarino et al., 2006), and preterm birth (PTB) (Feodor Nilsson et al., 2014; Miyake et al., 2014) have been linked to alcohol use, particularly at
high levels. Smoking is however a confounding factor for such outcomes and alcohol use in combination with smoking significantly increases the risk of for example PTB. A study of 1,565 Japanese women found that consumption of >1g alcohol per day more than doubled the risk of PTB (OR = 2.58, 95% CI: 1.004–5.80, p for trend = 0.003). In combination with smoking, the increase in the risk of PTB was more than fifteen-fold (OR = 15.11, 95% CI: 2.22–142.12) (Miyake et al., 2014). The risks of alcohol use at lower levels are not clear. A meta-analysis found no significant overall effect on LBW, SGA or PTB from alcohol when the analysis was restricted to studies that adjusted for confounders, such as smoking. The relative risk (RR) for LBW increased at around 10g of pure alcohol per day, just over one UK unit. At 52g per day, the RR increased two-fold and at 120g per day the risk of having a LBW baby was more than seven-fold, compared to non-drinkers. There was no increased risk of SGA at ≤10g per day. At 36g, just over four UK units, per day the RR for SGA was 1.39 (95% CI: 1.12–1.55) and thereafter the risk increased in a linear fashion. Finally, no increased risk for PTB was found <19g per day but a linear relationship was found from 36g per day, when the RR for PTB was 1.23 (95% CI: 1.05– 1.44) (Patra et al., 2011).
Another systematic review compared consumption of low to moderate levels of alcohol (less than 83g per week) with abstinence and found no significant association between low to moderate intake and birth defects, miscarriage, SGA, PTB, birth weight, still birth, or intrauterine growth restriction (IUGR). In fact, in some outcomes small amounts were related to a decreased risk. The authors suggested that this may be due to the ‘healthy drinker hypothesis’, in which women who have complications with their pregnancy are more likely to abstain (Henderson, Gray & Brocklehurst, 2007). Doi (2012) concluded from his systematic review that there was no evidence of risk for FASD, IUGR/SGA, LBW, PTB, chryptorchidism, or cognitive neurodevelopement at low levels of 8–16g per week or per occasion. Neither was there evidence for the risk of FASD or chryptochidism at moderate levels (24–48g per week or 24–4g per occasion). However, for heavy drinking (over 56g per week) and binge-drinking (over 48g per occasion) there was evidence of risk for FASD (heavy drinking), stillbirth, IUGR/SGA, LBW (heavy drinking), PTB, chryptochidism (binge drinking), cognitive neurodevelopment (heavy), and behaviour in neurodevelopment (Doi, 2012). A review of systematic reviews on risk of neurodevelopmental problems from alcohol use found that the risk increased at 70g per week (O’Leary & Bower, 2012). Furthermore, a meta-analysis of studies assessing pregnancy outcome (malformations) with moderate alcohol use (defined as up to 28g of
alcohol per week) showed no increased risks for malformations (OR = 1.00, 95% CI; 0.93– 1.08) (Polygenis et al., 1998). Overall, whilst negative effects are evident from the research, the picture is still unclear regarding cut-offs and whether there are levels of drinking that are free of risk.
2.3.2 Foetal Alcohol Spectrum Disorders
In the early 1970s, two American paediatricians diagnosed the first cases of an alcohol- related syndrome in new-borns, named Foetal Alcohol Syndrome (FAS) (Jones et al. 1973). Alcohol had previously been used in obstetrics for therapeutic properties to postpone premature labour, but observations of the risks of foetal apnoea and foetal death led to discontinuation of using alcohol for this purpose (Abel, 1981). The diagnoses of the first cases of FAS changed the perception on alcohol use during pregnancy to consider it a risk factor for poor pregnancy outcomes (Golden, 2005).
The FAS diagnosis includes three main domains; growth restrictions, craniofacial abnormalities, and damage to the central nervous system (CNS) (Jones, 2011; O’Leary, 2004; Larkby & Day, 1997). The diagnosis may also include confirmed maternal alcohol use, however diagnosis can be made if the three domains are present in the infant (Alberta Partnership on Foetal Alcohol Syndrome, 2003). In addition to the full FAS diagnosis, research also eventually found that “physical and neurobehavioral outcomes of prenatal alcohol exposure was variable, ranging from the classic form to a few minor abnormalities” (Calhoun & Warren, 2007, p. 169). In other words, it became evident that not all children exposed to alcohol in utero displayed all key features of the FAS diagnosis. These conditions have been identified as partial FAS (pFAS), Alcohol-Related Birth Defects (ARBD), and Alcohol-Related Neurodevelopmental Disorder (ARND) (Riley, Infante & Warren, 2011). ARND is characterised by CNS anomalies, whereas ARBD only includes physical anomalies, both of which require confirmation of maternal alcohol use. These conditions are included in the ‘umbrella term’ FASD, which covers the range of effects from mild cognitive and developmental impairment to the full FAS diagnosis (O’Leary, 2004).
Several factors are associated with the risk of giving birth to a child with FAS, including age, pattern of drinking, smoking, and timing of exposure. The first twelve weeks of pregnancy, the first trimester, are especially vulnerable due to the developmental processes taking place (O’Leary, 2004). Heavy drinking and alcohol consumption in binge-like
patterns are most harmful to the foetus (O’Leary, 2002), though factors such as low body mass index and inadequate nutrition further increases the risk (May et al., 2005). Howver, Abel and Hannigan (1995) noted that risk factors may vary between populations and samples of women. In terms of levels of drinking, Kesmodel (2016) in his literature review noted that “FAS and all the characteristics associated with it is by definition caused by
(high average daily) alcohol intake during pregnancy. To the extent that smaller amounts of alcohol are potentially harmful, the effects are likely to be the same but smaller” (p.164).
In relation to binge drinking, this review noted that the evidence is not clear on the harmful effects of binge drinking as a clear link has not been established and there is a lack of research on more specific timing of exposure from binge type patterns of drinking.
The prevalence of FAS varies between countries, within countries, fluctuates over time within the same populations, and depend on the availability diagnostic services (O’Leary, 2004). Difficulties in accurately estimating FAS relate partially to shortcomings in diagnostic services, but also to variations in data collection methods (Olsen, 2009). The three main methods for collecting data on FAS are passive surveillance, clinic-based studies, and active case ascertainment. Active case ascertainment studies have produced the highest prevalence rates of FAS, as they actively seek individuals that may have been exposed to alcohol in utero, and are commonly conducted in high-risk populations (May & Gossage, 2001). An overview of prevalence rates from international studies, using different methodologies, showed that the mean number of cases for FAS using surveillance methods was 0.845 per 1,000. In comparison, the prevalence in clinic-based studies was 1.83 per 1,000 and 15.61 per 1,000 in active case ascertainment studies (May et al., 2009). A more recent systematic review and meta-analysis aimed to estimate the global prevalence of FASD. Meta-analysis included samples from the general population (addressing the issues of bias mentioned above with higher prevalence in high-risk populations), found varying rates between countries. High prevalence of FAS was found in South Africa (55.42 cases per 1,000) and FASD was estimated to be 113.22 per 1,000. High levels of pFAS were found in Croatia (43.01 per 1,000). Heterogeneity in the studies included in the review was acknowledged and highlighted the need for greater methodologically consistency across prevalence studies (Roozen et al., 2016). In England, a 2011 study used hospital data to estimate the prevalence of FAS. Analysis of Hospital Episode Statistics, a passive surveillance method, showed FAS prevalence of 0.84 per 100,000 population, with regional variations from 0.41 per 100,000 to 1.67 per 100,000 population (Morleo, Cook & Bellis, 2011). In Sweden, data have shown that over an eight-
year period, only 300 individuals were diagnosed with FAS, it has been suggested that between 100 and 200 children per year fulfil the criteria for FAS (NBHW, 2015). Overall, underreporting is a recognised major issue in many countries, and thus the true prevalence is unknown (BMA, 2016).
From a public health perspective, the impact of FASD on the individual as well as society is significant. A systematic review of co-occurring comorbidities associated with FASD found an association with 428 conditions included in the International Classification of Disease (ICD-10). Physical conditions were among the most common conditions, including congenital malformations, but also behavioural or mental disorders (alcohol or drug abuse) Individuals with FASD require additional support throughout life, which creates high costs to society. The high number of co-existing conditions within the spectrum are all likely to increase costs in relation to health care and need for educational support (Popova et al., 2016). Estimates from Canada indicated that between 2008 and 2009, the direct costs on the healthcare system related only to the FAS diagnosis was $6.7 million (around £4.7 million) (Popova et al., 2012). However, there are also costs associated within the justice and correctional system, where individuals within the FASD spectrum are overrepresented (Popova et al., 2015).
While the true prevalence of FASD is not known, it is clear that this complex condition contributes to the burden of disease and more importantly creates issues for individuals throughout the life course. The wide range of health problems associated with FASD, as well as the high costs for society, emphasises the need for prevention. In addition, the issue of underreporting creates a clear need for better diagnostic services and consistent indicators.