Alcohol-related birth defects include cardiac and renal anomalies, orthopedic problems, and abnormalities of the eyes and ears (see Table 12-4). An association has further been reported between periconceptional alcohol use and omphalocele and gastroschisis (Richardson, 2011). here are no established sonographic criteria for prenatal diagnosis of fetal alcohol syndrome. hat said, in some cases, major abnormalities or growth restriction may be suggestive (Paintner, 2012).
Fetal vulnerability to alcohol is modiied by genetic components, nutritional status, environmental factors, coexisting maternal disease, and maternal age (Abel, 1995). The Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics have stressed that no amount of alcohol can be considered safe in pregnancy (Williams, 2015). Binge drinking, however, is believed to pose particularly high risk for alcohol-related birth defects and has also been linked to a higher risk for stillbirth (Centers for Disease Control, 2012; Maier, 2001; Strandberg-Larsen, 2008).
Traditionally, women with epilepsy requiring treatment with medication were informed that their risk for fetal malformations was increased. More recent data suggest that the risk may not be as great as once thought, particularly for newer agents. The most frequently reported anomalies are orofacial clets, cardiac malformations, and neural-tube defects.
Of agents in current use, valproic acid confers the greatest risk (Vajda, 2014). he North American Antiepileptic Drug (NAAED) Pregnancy Registry reported that major malformations developed in 9 percent of fetuses with irst-trimester valproate exposure. his included a 4-percent risk for neural-tube defects (Hernandez-Diaz, 2012). School-aged children with in utero exposure to valproic acid have poorer cognitive development-including signiicantly lower intelligence quotient (I) scores-than children exposed to other antiepileptic drugs (Bromley, 2014; Meador, 2009).
Regarding other speciic anticonvulsants, one recent metaanalysis identiied higher malformation rates among exposed children compared with rates among children born to women with untreated epilepsy. Rates were twofold higher among children exposed to carbamazepine or phenytoin, threefold higher among those exposed to phenobarbital, and fourfold higher among those exposed to topiramate as mono therapy (Weston, 2016). The risk for fetal malformations is approximately doubled if multiple agents are required (Vajda, 2016). Several older anticonvulsants also produce a constellation of malformations similar to the fetal hydantoin syndrome, which is described in
Figure 1i2-4.
FIGURE 12-4 Fetal hydantoin syndrome. A. Facial features including upturned nose, mild midfacial hypoplasia, and long upper lip with thin vermilion border. B. Distal digital hypoplasia. (Reproduced with permission from Buehler BA 1, Delimont D, van Waes M, et al: Prenatal prediction of risk of the fetal hydantoin syndrome, N Engl J Med. 1990 May 31;322(22):1567-1572.)
These risks do not appear to hold for the newer agents leve tiracetam and lamotrigine, although the number of reported pregnancies to date is smaller (M0Igaard-Nielsen, 2011;
Weston, 2016). The Motherisk Program reviewed eight stud ies of levetiracetam and concluded that mono therapy was associated with a 2-percent major malformation rate, which is no diferent from that for the general population (Chaudhry, 2014).