To compare interview data on drug use during pregnancy with data identified from a register of prescriptions.
We compared information from the Swedish Prescribed Drug Register with the Swedish Medical Birth Register on antidepressant use. In order to evaluate the clinical significance of the difference in ascertainment with the two methods, the rate of preterm births among singletons and of neonatal symptoms were studied.
During the year before the last menstrual period, 1.5% of the women filled prescriptions for antidepressants each month. Already before the pregnancy was known, the rate of filled prescriptions decreased and reached 0.5% towards the end of the pregnancy. Twenty-two percent of first-trimester use of antidepressants was unidentified using interview data and prescriptions during the 2nd and 3rd pregnancy months covered only 55% of actual use. When women who filled prescriptions 1 or 3 months before the last menstrual period were included, 17 and 43% respectively of women were included who probably did not use the drugs in the first trimester. Prescriptions gave a more complete ascertainment of drug use after the first trimester than data from antenatal care, which seemed to overestimate drug use.
Interview data seem to give the most valid results on early use. When interview data are not available, prescription data could be used, but should not include prescriptions given earlier than 1 month before the last menstrual period. Studies of drug use later in pregnancy are best based on prescription data in the absence of interview data.
Hypnotic benzodiazepine receptor agonists (HBRAs; zolpidem, zopiclone, and zaleplon) are used in the treatment of insomnia. Little is known about the safety of HBRAs during pregnancy.
Data from the Swedish Medical Birth Registry from July 1, 1995, up to 2007 were used to identify 1318 women who reported the use of HBRAs in early pregnancy. They gave birth to 1341 infants. Maternal characteristics and the presence of congenital malformations were compared with all other women who gave birth (n = 1,106,001) and all other infants (n = 1,125,734) born during the study period.
Use and/or reporting of HBRAs increased with maternal age and were higher at first than higher parity. Maternal smoking was strongly associated with reported use of HBRAs. The probability of using HBRAs increased in women who had had 3 or more earlier miscarriages or 5 or more years of involuntary childlessness. An excess use of other drugs and above all psychoactive drugs were seen in women reporting use of HBRAs.Hypnotic benzodiazepine receptor agonists were not associated with an increased risk for congenital malformations. A statistically significant high risk for other intestinal malformations than atresias/stenosis was based on only 4 infants.
Maternal use of HBRAs does not seem to increase malformation risk. The tentative association with some intestinal malformations may be due to chance because of multiple testing and needs confirmation.
An association between preterm birth and an increased risk of childhood asthma has been demonstrated, but the importance of intrauterine growth retardation on asthma risk is unclear. Using data from Swedish health registers, infant characteristics and childhood asthma were studied. Analyses were made using Mantel-Haenszel methodology with adjustment for year of birth, maternal age, parity, smoking in early pregnancy and maternal body mass index. Preterm birth, birth weight and birth weight for gestational week were analysed and childhood asthma was evaluated from prescriptions of anti-asthmatic drugs. Neonatal respiratory problems and treatment for them were studied as mediating factors. Both short gestational duration and intrauterine growth retardation appeared to be risk factors and seemed to act separately. The largest effect was seen from short gestational duration. Use of mechanical ventilation in the newborn period and bronchopulmonary dysplasia were strong risk factors. A moderately increased risk was also seen in infants born large for gestational age. We conclude that preterm birth is a stronger risk factor for childhood asthma than intrauterine growth disturbances; however, the latter also affects the risk, and is also seen in infants born at term.
Comment In: Eur Respir J. 2013 Nov;42(5):143124178938
Comment In: Eur Respir J. 2013 Nov;42(5):1430-124178937
To investigate a proposed association between in vitro fertilisation (IVF) and child asthma.
The risk for asthma after IVF was estimated as ORs using Mantel-Haenszel analysis.
The Swedish Medical Birth Register.
Of the 2 628 728 children born in 1982-2007 and surviving the perinatal period, 31 918 were conceived by IVF. Presence of asthma was defined as at least five prescriptions of antiasthmatic drugs during the period 1 July 2005-31 December 2009 according to the Swedish Prescribed Drug Register (115 767 children, 2323 of whom were born after IVF).
A significantly increased risk for asthma, albeit small, was found in children conceived by IVF (aOR 1.28, 95% CI 1.23 to 1.34), increasing the absolute risk from 4.4% to 5.6%. The risk increase for asthma was the same in boys and girls, in singletons and twins, and after caesarean section and vaginal delivery. The risk was higher for preterm than term singletons. For children with a low Apgar score, respiratory diagnoses, mechanical ventilation, continuous positive airway pressure or neonatal sepsis, the effect of IVF on asthma risk was low and statistically non-significant. Adjustment for length of involuntary childlessness eliminated the effect, and removal of infants whose mothers had used antiasthmatics in early pregnancy reduced the risk.
This study verifies an association between IVF and asthma in children. This can be partly explained by neonatal morbidity and by maternal asthma acting as mediators, but the main risk factor is parental subfertility. The mechanism for this is unclear.
To compare neonatal outcome of blastocyst and cleavage stage embryo transfers after IVF.
Births recorded in the Swedish Medical Birth Register after IVF performed, 2002-2006.
Treatments reported from all Swedish IVF clinics.
Some neonatal characteristics were compared in 1,311 infants born after blastocyst-stage transfer and 12,562 infants born after cleavage-stage transfer. Comparisons were also made with all births, 2002-2007 (n = 598,687).
After adjusting for year of birth, maternal age, parity, smoking habits, and body mass index, the risk of preterm birth among singletons was significantly greater after blastocyst-stage transfer than after cleavage-stage transfer. The risk of congenital malformations was also significantly higher. When the analysis was restricted to clinics where blastocyst transfers were made, the risk estimates increased for preterm birth, low birth weight, low APGAR score, and respiratory diagnoses, but did not change for congenital malformations.
The results indicate a small increase in risk associated with blastocyst transfer, perhaps owing to the longer period of in vitro culture. There is a possibility that this effect is due, at least in part, to a selection of women for blastocyst transfers. Further studies are needed either to verify or to refute the found associations.
BACKGROUND: Infants born after in vitro fertilization (IVF) differ from spontaneously conceived infants in a number of aspects which could increase the risk for future cerebral palsy (CP), e.g., multiple births, preterm births, neonatal complications. AIMS: To follow up children conceived by IVF with respect to risk for CP. METHODS: Infants born after IVF were identified from all IVF clinics in Sweden 1982-2007. Perinatal characteristics were obtained by linkage with the Medical Birth Register. The presence of CP in children born after IVF and in other children was identified from the Patient Register which contains diagnoses given at hospitalizations or specialist outpatient clinics. The risk for CP after IVF was studied after adjustment for year of birth, maternal age, parity, and smoking, all factors which co-vary both with IVF and with CP. Stratification was made for singletons and multiple births and for various neonatal outcomes. RESULTS: The adjusted odds ratio for CP after IVF was 1.81 (95% confidence interval, 95% CI 1.52-2.13), lower and not statistically significant when singletons or when unlike-sexed twins were analyzed. Stratification for various neonatal characteristics also reduced odds ratios to non-significant levels. For the last few years of the study (2004-2007) when the twinning rate after IVF was
We have previously demonstrated an association between neonatal phototherapy and/or neonatal icterus and risk of hospitalization for childhood asthma. This study included children who were prescribed anti-asthmatic medication on a population basis to study exposures during the foetal and neonatal period and risk of childhood asthma. The Swedish Medical Birth Register was linked to the Swedish Prescribed Drug Register. Perinatal data for singleton children who were prescribed anti-asthmatic medication (n = 61,256) were compared with corresponding data for all singleton children born in Sweden from 1 January 1990 to 30 June 2003 and surviving to 1 July 2005 (n = 1,338,319). Mantel-Haenszel's odds ratios were calculated after adjustment for various known confounders. Being the first-born child, maternal age above 44 yr, involuntary childlessness for more than 1 yr, maternal smoking during pregnancy, maternal diabetes mellitus of any kind, pre-eclampsia, caesarean section, and instrumental vaginal delivery were all associated with an increased prescription of anti-asthmatic medication during childhood. Preterm birth, low birth weight, being small for gestational age, respiratory problems, mechanical ventilation, and sepsis and/or pneumonia were also associated with increased drug prescriptions. Neonatal phototherapy and/or icterus were risk determinants for children who developed asthma before the age of 12. After controlling for confounders, the odds ratio for phototherapy and/or icterus remained at 1.30 (95% confidence interval 1.16-1.47). In conclusion, this large population-based study confirms an association between some maternal and perinatal factors and childhood asthma, including neonatal phototherapy and/or icterus.
BACKGROUND: The risk for congenital malformations is increased in infants born after in vitro fertilization (IVF). Some specific malformations appear to be more affected than others. METHODS: The presence of congenital malformations in 15,570 infants born after IVF with an embryo transfer between April 1, 2001, and the end of 2006 were compared with all infants born in Sweden during 2001 to 2007 (n = 689,157). Risk estimates were made after adjusting for year of birth, maternal age, parity, smoking, and body mass index. The risks of specific malformations were compared with data from a previous study (1982 to March 31, 2001) of 16,280 infants born after IVF. Different IVF methods were compared to respect to malformation risk. RESULTS: Increased risks of a similar magnitude were found for most cardiovascular malformations and limb reduction defects for both study periods. For neural tube defects, cardiac septal defects, and esophageal atresia, there was still an increased risk, but it was lower during the second than during the first period. For small bowel atresia, anal atresia, and hypospadias, the risk increase observed during the first study period had disappeared during the second period. An increased risk was seen for some syndromes that have been associated with imprinting errors. No difference in malformation risk according to IVF method was apparent. CONCLUSIONS: A slightly increased risk for congenital malformations after IVF persists. A decreasing risk is seen for some specific malformations, either true or the result of multiple testing.
Survival after malignancy has increased and the question of risks, including risk for congenital malformations for the offspring of these women has become important. Data on congenital malformations in such offspring are limited.
We compared congenital malformation in offspring, born 1994 to 2011 of women with a history of malignancy (at least 1 year before delivery) with all other offspring. Adjustment for confounders was mainly made by Mantel-Haenszel methodology. Data were obtained by linkage between Swedish national health registers.
We identified 71,954 (4.1%) infants with congenital malformation, of which 47,081 (2.7%) were relatively severe (roughly corresponding to major malformation). Among 7284 infants to women with a history of malignancy 204 relatively severe malformations were found (2.8%; odds ratio [OR] = 1.04; 95% confidence interval [CI], 0.91-1.20). After in vitro fertilization, the risk of a relatively severe malformation was significantly increased in women without a history of malignancy (OR = 1.31; 95% CI, 1.24-1.38) and still more in women with such a history (risk ratio = 1.85; 95% CI, 1.08-2.97). However, there were no significant differences neither, for any malformations (OR = 1.04; 95% CI, 0.92-1.16) nor for relatively severe malformations (OR = 1.04; 95% CI, 0.91-1.20), when comparing offspring only after maternal history of malignancy.
Background: The use of drugs for migraine during pregnancy may have adverse effects on delivery outcome, and warnings exist for such drugs regarding use during pregnancy. Most information in the literature concerns triptans. Objective: The aim of the study was to describe the delivery outcome when a woman had used drugs for migraine during pregnancy. Study Design: A register study where exposure for drugs was obtained partly by interview conducted by the attending antenatal care midwife and medical records from antenatal care (1995-2008) and partly by linkage to the Prescribed Drug Register (2005-8). Setting: All deliveries in Sweden (1?211?670 women) recorded in the Medical Birth Register with data from antenatal care. Patients: Women using triptans or ergots during pregnancy were identified and compared with all women who did not use drugs for migraine. Main Outcome Measures: Pregnancy complications, pregnancy duration and birthweight, neonatal morbidity and mortality, and congenital malformations. Results: Use of ergots or triptans during early pregnancy (first trimester) occurred in 3286 women with 3327 infants, while use after the first trimester occurred in 1394 women with 1419 infants. Women using such drugs for migraine were older than other women, were more often of parity 1 (no previous infant) and more often had a high body mass index. Women using drugs for migraine had not previously had more miscarriages than expected. There was an increased risk for pre-eclampsia (odds ratio [OR] 1.44; 95% CI 1.17, 1.76). An increased risk for preterm birth was seen after use of drugs for migraine later in pregnancy (OR 1.50; 95% CI 1.22, 1.84). There was no increased risk for stillbirth or early neonatal death. No certain signs of teratogenicity were found for any of the drug types when compared with women not using such drugs (OR for any malformation 0.95; 95% CI 0.80, 1.12). Conclusions: Our data suggest that the risk of adverse effects on pregnancy outcome associated with the use of drugs for migraine is low but data for triptans other than sumatriptan are still few.