Obstetrics and Gynecology International for instance, the risk increases at 30–34 years to 1.76 (95% CI 1.52–2.03) and at 40–44 years age to 6.66 (95% CI 1.94– 24.4). The eﬀect of maternal age will therefore depend on the speciﬁc malformation under study. Often the maternal age eﬀect on the use of drugs is strong. In Table 2, data for the use of antidepressant drugs in early pregnancy is shown as an example. The maternal age eﬀect on drug use varies markedly with the drug type [2]. Use of antiasthmatic drugs is, for example, more prevalent among women delivering at a young age (<25 years) than among older women while antihypertensives show the opposite distribution. If adequate adjustment for maternal age is not made, the estimated risk after maternal use of a drug may be falsely exaggerated or underestimated according to the directions of the age eﬀect on malformation risk and on the use of the drug. For the outcome of any congenital malformation the eﬀect is usually weak but for speciﬁc malformations it can be of greater importance. 3.4.2. Maternal Parity. The deﬁnition of the parity concept diﬀers. In this text, parity 1 means that the woman had her ﬁrst child and, for instance, parity 3 that she had two previous children (which could have been twins). Sometimes parity 0 or nulliparity is used for women at their ﬁrst delivery. The risk for any relatively severe congenital malformation (Table 2) is slightly higher at parity 1 than at higher parities but there is no change of risk between parities 2 and higher parities. For most speciﬁc malformations, the parity eﬀect is small. For esophageal and anal atresia, an increased risk at parity 1 is seen [5] but for cleft lip/palate, an increased risk at high parity seems to exist [6]. 3.4.3. Maternal Smoking and Use of Alcohol or Illegal Drugs in Early Pregnancy. The eﬀect of maternal smoking on the risk for infant malformation has been much discussed. According to Table 2, there is a weak eﬀect on any relatively severe congenital malformation with an odds ratio of less than 1.1. The eﬀect of smoking varies according to malformation type studied [7] but is much stronger for intrauterine growth and birth weight [8]. For cleft lip/palate the increased risk after maternal smoking is rather well established while data for many other conditions are scarce. As seen in Table 2, smoking is much more prevalent among women who use antidepressants and the same is true for the use of many other CNS active drugs. The speciﬁc relationship with diﬀerent drug groups can be found in [2]. One interesting such relation is with antihistamines where smoking is less prevalent than expected, notably for antihistamines used for nausea and vomiting in pregnancy (NVP). There are arguments suggesting that the relation is not explained by the fact that women with NVP stop smoking but that NVP is less prevalent among smoking women who get pregnant [9]. Adjustment for maternal smoking is thus at least some- times needed. Such adjustment can be made using a yes/no question but a quantitative estimate is often preferable, notably when the smoking eﬀect is strong. How detailed such a quantiﬁcation should be made depends on the available 5 possibilities. Often a division into smoking <10 cigarettes per day and 10 or more cigarettes per day is made as in Table 2. There is no convincing diﬀerence between the groups in the column for relatively severe malformations but deﬁnitely one in the column for antidepressant use. Also the use of other nicotine preparations may occur, for example, snuﬃng and nicotine applications for treatment of smoking addiction. Some evidence has been presented for a teratogenic eﬀect also at these administrations but no ﬁrm conclusions can yet be drawn and more data are needed. Hypoxia or carbon monoxide and not nicotine may cause the teratogenic action of maternal smoking [10]. In a few instances, maternal smoking appears to have a “protective” eﬀect with a lower malformation risk among infants of smokers than of nonsmokers, for example, neural tube defects and hypospadias [7]. The mechanism behind this is unclear. Complex addiction is common, and there is a strong association between smoking and alcohol use. The eﬀect of the use of large amounts of alcohol on the embryo is well known and can result in a recognizable “fetal alcohol syndrome” [11] in which presence of a cardiac defect is one component. A teratogenic eﬀect of moderate amounts of alcohol is more dubious [12]. Associations between alcohol use and some speciﬁc malformations like omphalocele and gastroschisis have been based on retrospective studies with a risk for recall bias [13]. Information on alcohol use in large numbers of individuals is diﬃcult to get from routine questionnaires or interviews, and eﬀorts to adjust for con- founding from alcohol use are therefore often ineﬀective. The importance of alcohol as a confounder obviously depends on the prevalence of alcohol use and abuse among pregnant women which probably varies much between diﬀerent popu- lations. Because of a strong association between smoking and alcohol use, adjustment for smoking (which is usually easier to get reliable data on) may take care of at least part of the confounding obtained by alcohol use. It is also diﬃcult to get information on the use of illegal drugs, notably in populations where such use is regarded as unacceptable social behaviour. Use of many of these drugs can have important eﬀects on pregnancy and infant mor- bidity but usually they are not very important confounders in studies of congenital malformations. It is true that some of these drugs have been associated with speciﬁc teratogenic eﬀects but these studies have been based on retrospective exposure data collection with a risk for recall bias [14]. 3.4.4. Body Mass Index. Increasing interest is being paid to the possible impact of the ongoing obesity epidemic in many parts of the world. Many ill eﬀects of prepregnancy obesity on pregnancy outcome has been found, including an increased risk for many (but not all) congenital malforma- tions [15]. As is seen in Table 2, there is a clear-cut increased risk in the risk for any relatively severe malformation and obesity is also associated with a strongly increased use of antidepressant drugs. Leanness, on the other hand, in general seems not to aﬀect malformation risk. The mechanism behind the eﬀect of obesity on malfor- mation risk is unclear. A possible explanation is that obesity