Bengt Källén

Background More than one-half of all pregnant women suffer from nausea and vomiting during pregnancy (NVP), primarily during the first trimester. Methods Prospectively ascertained information on drug use during pregnancy was obtained from the Swedish Medical Birth Register during the period July 1, 1995 to 2002. Antiemetics (antiemetic antihistamines, dopamine modulators, and ondansetron) primarily used for NVP were studied, and women reporting the use of these drugs were compared with all women who gave birth during the study period. Results Use of these antiemetics was reported in 4.5% of the pregnant women – 86% of whom reported their use before the first antenatal visit (usually weeks 10–12). Meclozine, followed by other antihistamines, accounted for 68% of the drugs reported. Young maternal age, multiparity, non-smoking, and a period of unwanted childlessness increased the probability of using any of the antiemetics during pregnancy. Women with a low education used these drugs more often than women with a relatively higher education. Neonates born to women who used any of the antiemetics had a reduced risk for low birthweight, prematurity, being small-for-gestational age, and having a malformation. No specific differences were observed with respect to the outcome following a comparison of different antiemetic drugs. Conclusions Women using antiemetics as a rule have a better delivery outcome than other women, probably due to an effect of a well-functioning placenta, which is associated with NVP. There were no signs of any significant teratogenicity of the drugs studied, but for some drugs the number of exposures was low.

Background.  Deliveries among women who had an in vitro fertilization (IVF) are characterized by increased risks for both the mother and the infant/child. Part of these effects may be due to maternal characteristics.Methods.  Using reports from all clinics performing IVF in Sweden, 12 186 women who gave birth after such procedures were identified (13 261 deliveries, 16 280 infants born). Various social and medical characteristics of the women were studied and compared with all women giving birth. Information was retrieved by interviews in early pregnancy or by linkage with various registers.Results.  Women who had IVF were older than other women who gave birth and were older after standard IVF than after intracytoplasmatic sperm injection (ICSI). They were more often of first parity and smoked less than other delivered women. There were more women with high body mass index: they worked outside home less often and were more often of Swedish nationality. Women who had standard IVF had more previous miscarriages than expected, but this was not true for women who had ICSI. Their pattern of drug usage differed from that of other women who had given birth.Conclusions.  Women who underwent IVF and gave birth showed marked deviations from other women who gave birth. Some of these characteristics may help to explain the increased risks associated with these procedures. Women who had ICSI were less deviating than women who had standard IVF.

Objective: To test the hypothesis that maternal drug use or treatment for infertility is related to the occurrence of infant craniostenosis.Design and Material: Maternal drug use and infertility treatment were studied in 398 cases of craniostenosis, identified from various Swedish health registers. Exposure information was ascertained in early pregnancy, and comparisons after adjustment for some confounders were made with all infants born. In order to validate some findings, data from the Central-East France Registry were studied for first trimester drug exposure in 235 infants, and use of ovarian stimulation in 315 infants with craniostenosis.Results: A statistically significant association between maternal use of anticonvulsants and infant craniostenosis was found (risk ratio [Swedish data], 6.9; 95% confidence interval, 1.10 to 7.94). With the Swedish data, an association was found with three nitrosatable drugs (risk ratio, 3.4; 95% confidence interval, 1.10 to 7.94), previously associated with the occurrence of craniostenosis, but this was based on only five exposures, and no such exposure occurred in the French data set. No association with subfertility (odds ratio, 0.72; 95% confidence interval, 0.60 to 1.86) or infertility treatment (odds ratio, 1.06; 95% confidence interval, 0.60 to 1.87) was found in the Swedish data and no statistically significant increase in the use of ovulation stimulation in the French data.Conclusions: A strong association was found between the maternal use of anticonvulsants and infant craniostenosis, and a tentative association was found with the use of nitrofurantoin and two other nitrosatable drugs. There was no association with maternal subfertility or infertility treatment.

ABSTRACT The review presented here discusses and exemplifies problems in epidemiological studies of drug teratogenesis according to methodology: case–control studies, cohort studies, or total population studies. Sources of errors and the possibility of confounding are underlined. The review stresses the caution with which conclusions have to be drawn when exposure data are retrospective or other possible bias exists. It also stresses the problem with the multiple testing situation that is usually present in the studies. It is therefore difficult to draw any firm conclusion from single studies and still more difficult to draw conclusions on causality. As randomized studies are in most cases out of the question, one has to rely on the type of studies which can be made, but the interpretation of the results should be cautious. The ideal study, next to a randomized one, is a large prospective study with detailed exposure information and detailed and unbiased outcome data. Even so, such a study can mainly be used for identifying possible associations which have to be verified or rejected in new studies. Nearly every finding of a risk increase, if not extremely strong, should only be regarded as a tentative signal to be tested in independent studies.

In Sweden 17 hospitals or private clinics perform in vitro fertilisation. The National Board of Health and Welfare requested information from these laboratories on all women who had undergone in vitro fertilisation and who had had a baby or whose pregnancy outcome was not known. By linking these data with the Swedish medical birth register, we identified infants born from 1982 to 2001.1 2 This register covers nearly all deliveries in Sweden and is based on copies of medical documents from the antenatal care, the delivery, and the paediatric examination of newborn infants.

Infants with a clinical diagnosis of anophthalmia or microphthalmia were identified from four health registers in Sweden, covering different parts of the period 1965–2001. During the observation period, the rate of anophthalmia decreased from the early 1970s from 0.4 to 0.2 per 10,000 births. The registered rate of microphthalmia increased markedly during the observation period to reach a maximum in 1987 of about 1.5 per 10,000. About 10% of the 432 identified children had a chromosome anomaly. There was no geographical variation in prevalence and infants born in urban or rural districts had, if anything, a lower risk than infants born in cities (0.93 and 1.13 per 10,000, respectively). Non-eye malformations were more common at anophthalmia (63%) than at microphthalmia (30%). Sex ratio was normal and no statistically significant variation between sub-groups (anophthalmia, microphthalmia, isolated, associated with non-eye malformations) could be demonstrated. There was a marked risk increase with maternal age but no certain parity effect, no effect of maternal education, but a possible association with subfertility. Maternal smoking in early pregnancy seemed to increase the risk for anophthalmia or microphthalmia in the absence of a coloboma.