Maternal drug use during pregnancy and asthma risk among children.

BACKGROUND: Maternal use of some drugs, notably paracetamol and drugs for gastroesophageal reflux, has been associated with an increased risk of childhood asthma in the child. We wanted to analyze these associations with consideration to the confounding of maternal asthma. METHODS: Childhood asthma was identified from the Swedish National Prescription Register and maternal drug use during the latter part of pregnancy from antenatal records, computerized in the Swedish Medical Birth Register. Risks were estimated as odds ratios (OR) with 95% confidence intervals, using Mantel-Haenszel technique with adjustment for year of birth, maternal age, parity, smoking habits, and BMI. RESULTS: A statistical association between maternal use of many different drugs, including paracetamol, and childhood asthma existed but was mainly due to concomitant drug use, related to maternal asthma. The only associations that appeared to be true were with drugs for gastroesophageal reflux (adjusted (OR) = 1.32, 95% CI, 1.18-1.54) and with opiates (adjusted OR = 1.56 (96% CI, 1.05-2.34). CONCLUSIONS: Maternal use of paracetamol did not seem to increase the risk of childhood asthma, but the previously described association with drugs for gastroesophageal reflux was supported. The analysis is complicated by the confounding from maternal asthma.

Association between preterm birth and intrauterine growth retardation and child asthma.

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.

Asthma in Swedish children conceived by in vitro fertilisation.

OBJECTIVES: To investigate a proposed association between in vitro fertilisation (IVF) and child asthma. DESIGN: The risk for asthma after IVF was estimated as ORs using Mantel-Haenszel analysis. SETTING: The Swedish Medical Birth Register. PATIENTS: 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). RESULTS: 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. CONCLUSIONS: 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.

Apgar scores at 5 minutes after birth in relation to school performance at 16 years of age.

OBJECTIVE: To estimate the association between an Apgar score of less than 7 at 5 minutes after birth and long-term cognitive function. METHODS: A linkage between the Swedish Medical Birth Registry and the Swedish School Grade Registry was performed. All singletons born from 1973 to 1986 after 36 6/7 weeks of gestation to Swedish-born women were included. Fetuses that were stillborn, newborns who had congenital malformations or were small for gestational age, and children who died or emigrated before 16 years of age were excluded from the analysis. RESULTS: The study included 877,618 individuals in the analysis. Newborns with Apgar scores less than 7 at 5 minutes after birth showed a significantly increased risk of never receiving graduation grades, presumably because they went to special schools because of cognitive impairment or other special educational needs (odds ratio 1.93, 95% confidence interval 1.75-2.14). One out of 44 newborns (numbers needed to harm) with an Apgar score of less than 7 at 5 minutes after birth will go to a special school because of the antenatal or perinatal factors that caused the low Apgar score. Nearly all school children who had Apgar scores of less than 7 at 5 minutes after birth showed an increased risk of graduating from compulsory school without graduation grades in that specific subject or receiving the lowest possible grades and were also less likely to receive the highest possible grade. CONCLUSION: An Apgar score of less than 7 at 5 minutes after birth is associated with subtle cognitive impairment, as measured by academic achievement at 16 years of age. LEVEL OF EVIDENCE: II.

Delivery outcome after maternal use of drugs for migraine: a register study in Sweden.

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.

Is there an increased risk for drug treated attention deficit/hyperactivity disorder in children born after in vitro fertilization?

BACKGROUND: There is mounting evidence that children born after in vitro fertilization (IVF) run an increased risk of neurological complications and notably cerebral palsy. Whether developmental disturbances occur more often than expected is debated. AIM: To investigate the risk for ADHD in children conceived after IVF. METHODS: Children conceived after IVF and born between 1982 and 2005 were identified from all IVF clinics in Sweden. Children who developed attention deficit/hyperactivity disorder (ADHD) were identified with the use of a register over all prescribed drugs in Sweden, using prescriptions for methylphenidate or atomixetine as indicators of ADHD. Maternal and neonatal characteristics were obtained by linkage with the Medical Birth Register and relevant confounders were adjusted for using Mantel-Haenszel procedures. We studied 28 158 children born after IVF and compared them with 2 417 886 children in the population. RESULTS: After adjustment for year of birth, maternal age, parity, smoking, BMI, and maternal education and after exclusion of women who did not cohabit, a weak but statistically significant association was found with an odds ratio=1.18, 95% confidence interval 1.03-1.36. The effect was stronger in girls (OR=1.40) than boys (OR=1.11) but this difference could be random. After adjustment for length of involuntary childlessness, the OR decreased slightly and lost statistical significance. CONCLUSIONS: The study suggests a weak association between IVF and drug treated ADHD.

The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research.

Swedish health care and national health registers are dependent on the presence of a unique identifier. This paper describes the Swedish personal identity number (PIN) and explores ethical issues of its use in medical research. A ten-digit-PIN is maintained by the National Tax Board for all individuals that have resided in Sweden since 1947. Until January 2008, an estimated 75,638 individuals have changed PIN. The most common reasons for change of PIN are incorrect recording of date of birth or sex among immigrants or newborns. Although uncommon, change of sex always leads to change of PIN since the PIN is sex-specific. The most common reasons for re-use of PIN (n = 15,887), is when immigrants are assigned a PIN that has previously been assigned to someone else. This is sometimes necessary since there is a shortage of certain PIN combinations referring to dates of birth in the 1950s and 1960s. Several ethical issues can be raised pro and con the use of PIN in medical research. The Swedish PIN is a useful tool for linkages between medical registers and allows for virtually 100% coverage of the Swedish health care system. We suggest that matching of registers through PIN and matching of national health registers without the explicit approval of the individual patient is to the benefit for both the individual patient and for society.

Maternal use of antihypertensive drugs in early pregnancy and delivery outcome, notably the presence of congenital heart defects in the infants.

PURPOSE: To investigate the association between maternal use of antihypertensives in early pregnancy and delivery outcome, notably infant congenital malformations. METHODS: A cohort study of 1,418 women who had used antihypertensive drugs in early pregnancy but had no diabetes diagnosis were identified from the Swedish Medical Birth Register. RESULTS: There was an excess risk for placental abruption, caesarean section, delivery induction, and post-delivery hemorrhage in women taking hypertensives. Infants were more often than expected born preterm, were small for gestational age, and had an excess of various neonatal symptoms. Cardiovascular defects occurred with an adjusted odds ratio of 2.59 (95% CI 1.92-3.51). The results were similar when the woman had used ACE inhibitors or other antihypertensives, notably beta blockers. Stillbirth rate was increased (risk ratio 1.87, 95% CI 1.02-3.02), again without any clear drug specificity. CONCLUSIONS: There seems to be little drug specificity in the association between maternal use of antihypertensives and an increased risk for infant cardiovascular defects.

Maternal use of loperamide in early pregnancy and delivery outcome.

AIM: To study delivery outcome including presence of infant congenital malformations after maternal use of loperamide in early pregnancy. METHODS: Using the Swedish Medical Birth Register, women reporting the use of loperamide in early pregnancy were compared with other women for the period July 1, 1995-2004. Odds ratios (OR) or risk ratios (RR) were estimated after adjustment for some variables, which were associated with the use of loperamide (year of delivery, maternal age, parity, smoking, number of previous miscarriages). RESULTS: Characteristics of women using loperamide in early pregnancy were identified. An analysis of concomitant drug use indicated that only few of the women had inflammatory bowel disease. The risk of any congenital malformation was increased (OR = 1.43, 95% CI 1.04-1.96), based on 43 cases, but no major contributing type could be identified. The risk of hypospadias was significantly increased (RR = 3.2, 95% CI 1.3-6.6), based on seven cases. A statistically significant increase was seen also for placenta previa, large for gestational age and caesarean section. CONCLUSION: Maternal use of loperamide in early pregnancy may be associated with a moderate risk increase for a malformation in the infant. The finding should be evaluated from other large studies.

Use of anti-asthmatic drugs during pregnancy. 3. Congenital malformations in the infants.

OBJECTIVE: To study the risk for congenital malformations among infants whose mothers used anti-asthmatic drugs during pregnancy. MATERIALS AND METHODS: We studied 24,750 infants whose mothers reported the use of anti-asthmatic drugs in early pregnancy. Infants were identified from the Swedish Medical Birth Register where drug use reported at the first maternal health care visit is recorded. Congenital malformations among the infants born were identified from that register, the Swedish Register of Congenital Malformations, and the Hospital Discharge Register. Rates of malformations among infants exposed to anti-asthmatics were compared with the background population rate of malformations (4.7%) after adjustment for year of birth, maternal age, parity, smoking, and previous miscarriages. RESULTS: A weak increase in the risk for a congenital malformation was seen (odds ratio =1.09, 95% CI=1.03-1.15) which could not be explained by the confounders studied. The risks for three specific types of malformations appeared to be increased: relatively severe cardiac defects, orofacial clefts and specifically median cleft palate, and anal atresia. For the two last mentioned groups, use of anti-asthmatics with inhaled corticosteroids showed a higher odds ratio than use of other anti-asthmatics, but the differences could be random. CONCLUSIONS: Maternal asthma and use of anti-asthmatic drugs carry no major risk for congenital malformations in the offspring, but a slight teratogenic effect cannot be excluded. It may be due to asthma, and arguments for a stronger effect of inhaled corticosteroids than of other anti-asthmatics are weak.

Use of anti-asthmatic drugs during pregnancy. 2. Infant characteristics excluding congenital malformations.

OBJECTIVE: To study the characteristics of the infants born to women who have used anti-asthmatic drugs during pregnancy. MATERIAL AND METHODS: Various characteristics of infants with mothers who had reported the use of anti-asthmatic drugs in early pregnancy (n=24,750) or had such drugs prescribed later during pregnancy by a maternity health care centre (n=763) were identified from the Swedish Medical Birth Register and compared to those of all infants. Risks estimated with Mantel-Haenszel technique were expressed as odds ratios (OR) with 95% confidence intervals after adjustment for a number of putative confounders. The severity of maternal asthma was assessed on the basis of the number of anti-asthmatic drugs used. RESULTS: An increased risk for preterm birth, low birth weight and small for gestational age was found, which increased with the number of anti-asthmatic drugs used by the mother during pregnancy (OR=1.46, 1.67, and 1.70, respectively, when three or more drugs had been used). An increased risk for large for gestational age could be explained by the effect of gestational diabetes and high body mass index. An increased risk for neonatal icterus was mainly an effect of preterm birth, while an increased risk for respiratory problems and/or low Apgar score (OR=1.43) was only slightly reduced in full-term infants. An increased risk for hyperglycaemia (OR=1.62) was not explained by confounding from maternal diabetes. No risk increase was found for neonatal convulsions or cerebral haemorrhage. Mortality was increased only among infants whose mother had used three or more anti-asthmatic drugs (OR=1.52). CONCLUSION: Infants whose mothers had asthma had a number of manifestations of poor outcome which appeared to be linked with the severity of the asthma.

Use of anti-asthmatic drugs during pregnancy. 1. Maternal characteristics, pregnancy and delivery complications.

OBJECTIVE: To study, in a large cohort, the association between the use of anti-asthmatic drugs during pregnancy and pregnancy complications. METHODS: Using the Swedish Medical Birth Register, we identified 24,369 women who reported the use of anti-asthmatic drugs in early pregnancy and 7778 women who were prescribed such drugs later during pregnancy by antenatal care system centres, during the period July 1, 1995 up to and including 2004. We studied maternal characteristics and pregnancy and delivery complications. Comparisons were made with all women having given birth to a child recorded in the register during this period. RESULTS: Women using anti-asthmatic drugs were characterized by a young maternal age, low parity, increased rate of smoking, low education, and high body mass index. An association with subfertility was also observed. Pre-existing diabetes did not occur in excess. A number of pregnancy and delivery complications occurred at an increased rate with the use of anti-asthmatic drugs, notably when three or more such drugs had been used: gestational diabetes [odds ratio (OR)=1.59], preeclampsia (OR=1.44), haemorrhage at delivery (OR=1.32) and premature rupture of membranes (OR=1.59); no excess of placenta abruption or previa was found. Primary weak contractions occurred more often than expected in women that used anti-asthmatic drugs (OR=1.15), and this was tentatively linked to the use of beta-2 adrenergic agonists. Most of the increased risk for caesarean section (OR=1.79) could be explained by these pregnancy complications. An increased risk for delivery induction (OR=1.74) was found among deliveries that did not start with a caesarean section. CONCLUSION: An increase risk of pregnancy complications occurs with the use of anti-asthmatic drugs by pregnant women, which results in an increased rate of caesarean sections.

Maternal use of selective serotonin re-uptake inhibitors in early pregnancy and infant congenital malformations.

BACKGROUND: Maternal use of selective serotonin re-uptake inhibitors (SSRIs) has recently been associated with an increased risk for certain malformations. METHODS: Using the Swedish Medical Birth Register, we identified women who had reported the use of SSRIs in early pregnancy and studied their infants, born between July 1, 1995 and the end of 2004. Congenital malformations were identified from that register, from the Register of Congenital Malformations, and from the Hospital Discharge Register. The effect of drug exposure was studied after adjustment for a number of identified maternal characteristics that could act as confounders. RESULTS: We identified 6,481 women who reported the use of SSRIs in early pregnancy and their 6,555 infants. There was no general increase in malformation risk. An increased risk for cystic kidneys was seen, but this was based on only nine malformed infants, and the pathology varied between these cases. An in-depth study of cardiovascular defects identified an association between such defects and notably ventricular and atrial septum defects and maternal use of paroxetine but not other SSRIs. No support for a postulated association between SSRI use and infant craniostenosis or omphalocele was found. CONCLUSIONS: Use of SSRIs in early pregnancy does not seem to be a major risk factor for infant malformations. The association between paroxetine use and infant cardiovascular defects may be a result of multiple testing, but is supported by other studies.

The new Swedish Prescribed Drug Register--opportunities for pharmacoepidemiological research and experience from the first six months.

PURPOSE: To describe the content and potentials of the new Swedish national register on prescribed and dispensed medicines. METHODS: The Swedish Prescribed Drug Register contains information about age, sex and unique identifier of the patient as well as the prescriber's profession and practice. Information regarding drug utilization and expenditures for prescribed drugs in the entire Swedish population was extracted from the first six months July-December 2005 and compared with total drug sales in the country including OTC and hospital use. RESULTS: The total quantity of drugs sold in Sweden was 2666 million DDDs, corresponding to 1608 DDD/1000 inhabitants daily. The total expenditures were 1.6 billion Euro. The prescribed drugs, included in the register, accounted for 84% of the total utilization and 77% of the total expenditures. About half of all men and two-thirds of all women in the country purchased drugs. The proportion increased by age. The most common drugs for chronic treatment were diuretics among women (8.8% of the population) and antithrombotic agents among men (7.6%). Psychotropic drugs, corticosteroids and analgesics were more common among women, while men used antithrombotic agents, antidiabetic drugs, lipid lowering agents and ACE inhibitors to a greater extent. CONCLUSIONS: The new register provides valuable data on exposure to drugs and is useful to study patterns of drug utilization. The possibilities for record linkage to other health registers gives from an international perspective good opportunities to explore drug and disease associations and the risks, benefits, effectiveness and health economical effects of drug use.

Size of delivery unit and neonatal outcome in Sweden. A catchment area analysis.

BACKGROUND: Quality of perinatal care was evaluated in relation to size of delivery unit and size of catchment area for deliveries. METHODS: Neonatal outcome, measured as neonatal mortality, low Apgar scores at 5 min, and the occurrence of respiratory disorders and cerebral palsy was analyzed during a 15-year period from 1985 to 1999 inclusive. Figures were derived from the Swedish Medical Birth Registry and the Hospital Discharge Registry. Odds ratios were estimated for the different outcomes in relation to size of delivery unit (actual and estimated number of births) and the provision of a pediatric department at the hospital. Seven possible confounders were considered: year of birth, maternal age, parity, smoking during pregnancy, gestational age, parental cohabitation, and maternal body mass index. RESULTS: Neonatal mortality was significantly higher for infants in families living within the catchment area of the smallest units without a pediatric department. Small differences in the occurrence of respiratory disturbances and Apgar scores are probably due to diagnostic differences. There were no differences in the incidence of cerebral palsy. Neonatal mortality continued to decrease during the observation period. CONCLUSIONS: Differences were minor, pointing to a fairly homogeneous quality of perinatal care and an efficient referral system for risk pregnancies. Mortality continues to decrease in spite of a reduction in the number of units caring for deliveries.

In vitro fertilization in Sweden: maternal characteristics.

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.

Hospital level of care and neonatal mortality in low- and high-risk deliveries: reassessing the question in Sweden by multilevel analysis.

BACKGROUND: In high-risk births, the availability and concentration of neonatal resources in larger regional hospitals increases the chance of survival. The advantages of regionalization for low-risk deliveries are still unclear, but some studies have suggested that regionalization also is beneficial for low risk deliveries. The aim of the present study was to investigate both the relevance of regionalization and the concentration of neonatal resources as determinants of mortality in low- and high-risk deliveries in Sweden. METHODS: Interhospital differences in 28-day neonatal mortality were analyzed distinguishing maternal and delivery factors from institutional ones. Using information from the Swedish Birth Register (1990-1995), we performed risk-stratified multilevel logistic regression analysis to study 691,742 births (first level) nested within the 66 Swedish hospitals with maternity wards (second level). RESULTS: In low-risk deliveries, mortality decreased with improved access to neonatal resources. Mortality was lowest in larger regional hospitals with full access to neonatal care. This association remained unchanged after adjusting for patient mix. With regard to high-risk deliveries, mortality was higher in large county and regional hospitals than in small hospitals without access to neonatal care but, as expected, this increased risk disappeared after adjustment for patient mix. CONCLUSIONS: Increased regionalization and concentration of neonatal resources for low-risk births is justified from a strictly medical point of view. From a public health perspective, closing small obstetrics units may prevent an appreciable number of deaths, but it would have only a very small impact on the risk of mortality from the individual's point of view. The cost-effectiveness of such a step remains to be analyzed from a health economics perspective.

In vitro fertilisation in Sweden: obstetric characteristics, maternal morbidity and mortality.

OBJECTIVE: To investigate obstetric characteristics, maternal morbidity and mortality among Swedish women giving birth after in vitro fertilisation (IVF) treatment. DESIGN: Register study. SETTING: Nationwide study in Sweden. SAMPLE: All women known to have had IVF in Sweden 1982-2001. METHODS: Using Swedish health registers, women who had given birth after IVF were identified from all Swedish IVF clinics and compared with all women who gave birth. Analysis was performed with the Mantel-Haenszel technique. MAIN OUTCOME MEASURES: Diagnoses during pregnancy, at delivery and at re-admission within 60 days after delivery and risk of cancer. RESULTS: IVF women had an increased risk of bleeding in early pregnancy [odds ratio (OR) = 4.59, 95% confidence interval (95% CI) 4.08-5.15] and of ovarian torsion during pregnancy (OR = 10.6, 5.69-10.7). They were also more likely to encounter pre-eclampsia (OR = 1.63, 1.53-1.74), placental abruption (2.17, 1.74-2.72), placenta praevia (3.65, 3.15-4.23), bleeding in association with vaginal delivery (1.40, 1.38-1.50) and premature rupture of membranes (PROM) (2.54, 2.34-2.76). Interventions including caesarean sections (1.38, 1.32-1.43) and induction of labour (1.37, 1.29-1.46) in singleton pregnancies was more frequent. The type of IVF method had little effect on these results, but there was a tendency for women who had received intra-cytoplasmatic sperm injection (ICSI) to have slightly fewer complications than women having standard IVF. There was a significant decrease in cancer risk after IVF (0.79, 0.69-0.91) but a suggested increase in the risk of ovarian cancer both before (2.70, 1.49-4.91) and after (2.08, 1.15-3.76) IVF. No change in mortality was observed. CONCLUSIONS: Women treated with IVF had an increased obstetric morbidity. This seems to contribute little to the well-known increased risk of preterm delivery.

Is erythromycin therapy teratogenic in humans?

The possible teratogenic effect of erythromycin therapy, noted previously, was studied. Women who had taken erythromycin or penicillin V in early pregnancy and their infants were studied, using the Swedish Medical Birth Register where information on drug use during pregnancy was recorded based on interviews in early pregnancy. The risk for any congenital malformation after erythromycin therapy (but not after penicillin V therapy) was increased (odds ratio 1.24, 95% confidence interval: 1.01-1.51) and this was due to an effect on cardiovascular malformations (odds ratio 1.92, 95% CI: 1.37-2.68). There was also an indicated increased risk for pyloric stenosis (risk ratio 3.0, 95% CI: 1.1-8.5 after exposure in early pregnancy). Various explanations to the finding are discussed, one of them linked to the fact that erythromycin inhibits a specific cardiac potassium channel (IKr) which seems to play a major role in cardiac rhythm regulation in the early embryo. Potent blocking drugs cause as a class effect cardiac defects in animal experiments.