Prematurity and neonatal outcome including congenital malformations after maternal malignancy within six months prior to or during pregnancy.

INTRODUCTION: The proportion of women who postpone childbearing is increasing. As malignancy risk increases with age, pregnancy in connection with malignancy will become more common. MATERIAL AND METHODS: We compared infants born 1994-2011 to women with a malignancy within six months prior to the last menstrual period or during pregnancy with offspring of women without a previous malignancy. Five national registers were used. RESULTS: A total of 790 women with a malignancy diagnosis from six months prior to the last menstrual period up to delivery were identified. Their 802 infants were compared with 1 742 757 infants of women without a malignancy. A high rate of prematurity was found, especially when the malignancy was diagnosed during the second or third trimesters (33%). Most of these premature births were the result of induced delivery before 35 weeks (91%). The most remarkable finding is the observation that these premature infants had a significantly higher risk for neonatal morbidity than premature infants in the control group with an adjusted odds ratio of 2.67 (95% confidence interval; 1.86-3.84). We found a significantly increased risk of mainly relatively mild malformations among infants of women with a malignancy diagnosis within six months prior to the last menstrual period or during the first trimester with a risk ratio of 1.81 (95% confidence interval; 1.20-2.61). CONCLUSIONS: A high incidence of prematurity, mostly due to induced delivery, was found, including an increased risk for neonatal morbidity among these infants. An increased risk for relatively mild malformations was also found.

Congenital malformations in offspring of women with a history of malignancy.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: No general increase in malformation rate was found in infants born to women with a history of malignancy. A previously known increased risk after in vitro fertilization was verified and it is possible that this risk is further augmented among infants born of women with a history of malignancy. Birth Defects Research 109:224-233, 2017. © 2016 Wiley Periodicals, Inc.

Characteristics of the Offspring of Women with a History of Malignancy, Excluding Congenital Malformations.

OBJECTIVE: To study the characteristics (except congenital malformations) of offspring born to women with a history of malignancy. METHODS: Data were obtained by linkage between four different Swedish national health registers. We compared the offspring born between 1994 and 2011 of women with a history of malignancy with all other infants. Survival of the infants was followed up through 2013. Adjusting for confounders was performed using Mantel-Haenszel methodology. We identified 7315 infants born to women with a history of a malignancy diagnosed at least 1 year before delivery. The total number of deliveries in Sweden in these years was 1 746 870, with 1 780 112 infants being born. We assessed rates of intrauterine death, preterm birth, low birth weight, and the nature of intrauterine growth. We also examined neonatal diagnoses (asphyxia, chronic respiratory condition, intracranial hemorrhage, jaundice, hypoglycemia, CNS symptoms) and infant death. RESULTS: In women with a history of malignancy, we found no significantly increased risk for stillbirth or infant death. There were elevated rates of preterm birth (OR 1.50, 95% CI 1.37 to 1.64), very preterm birth (OR 1.89, 95% CI 1.54 to 2.32), and low birth weight (OR 1.50, 95% CI 1.34 to 1.68). There was a significantly increased risk of birth asphyxia, jaundice, hypoglycemia, and low Apgar score among infants born to women with a history of malignancy (OR 1.24, 95% CI 1.15 to 1.33), and this risk was maintained after excluding infants born after IVF. CONCLUSION: We found an increased risk of preterm birth and low birth weight among infants of women with a history of malignancy, and as a result, found an increased risk of neonatal morbidity. No significant increase in risk of intrauterine or postnatal death was noted.

Deliveries After Malignant Disease Before Pregnancy: Maternal Characteristics, Pregnancy, and Delivery Complications.

PURPOSE: Survival after cancer has increased, and the question of risks in later pregnancies has become important. A previous malignancy may affect pregnancy outcome. METHODS: Comparison of women with malignant disease before pregnancy with all other women giving birth during 1994-2011. Data were obtained by linkage between Swedish national health registers. Subfertility, evaluated as time to pregnancy, and in vitro fertilization (IVF) before the relevant delivery were studied. The following delivery diagnoses were studied: gestational diabetes, preeclampsia, placenta previa, placenta abruption, placenta retention, bleeding around delivery, and premature rupture of membranes. The rates of cesarean section and vacuum extraction or forceps delivery were also studied. RESULTS: We identified 3931 women with 7176 deliveries and with a malignancy diagnosed at least 1 year before the delivery. The total number of deliveries in Sweden in these years was 1,746,870. Overall, an increased risk of subfertility (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.07-1.28), use of IVF (OR = 1.36, CI 1.21-1.53), delivery complications (OR = 1.17, 95% CI 1.10-1.24), and rate of caesarean sections (OR = 1.27, 95% CI 1.20-1.34) was observed among women with a history of malignancy compared with other women. CONCLUSION: We found an increased risk of subfertility, pregnancy, and delivery complications in women with a history of malignant disease. Further studies are needed to evaluate the risks of specific treatments and to provide these women with reliable information that could affect their family planning.

Use of ondansetron during pregnancy and congenital malformations in the infant.

The study investigates teratogenic risks with ondansetron (Zofran(®)). Data from the Swedish Medical Birth Register combined with the Swedish Register of Prescribed Drugs were used to identify 1349 infants born of women who had taken ondansetron in early pregnancy, 1998-2012. Presence of congenital malformations in the offspring was identified with three national health registers. In a Mantel-Haenszel analysis adjustment was made for year of delivery, maternal age, parity, smoking in early pregnancy and pre-pregnancy body mass index. Risks were expressed as odds or risk ratios with 95% confidence intervals. No statistically significantly increased risk for a major malformation was found. The risks for a cardiovascular defect and notably a cardiac septum defect were increased and statistically significant (OR=1.62, 95% CI 1.04-2.14, and RR 2.05, 95% CI 1.19-3.28, respective). The teratogenic risk with ondansetron is low but an increased risk for a cardiac septum defect is likely.

The risk of neurodisability and other long-term outcomes for infants born following ART.

Children born after assisted reproductive technologies (ART) have an increased morbidity. The risk of developing cerebral palsy is nearly doubled and the risk of developing epilepsy is also higher. Behavioural problems including attention deficit/hyperactivity disorder may be more common in children born following ART than among naturally conceived children but the finding is uncertain. Data on autism are difficult to interpret. There may exist a small increase in the incidence of childhood cancer and there is greater evidence of an elevated risk of asthma. To some extent, these risks are mediated by neonatal complications including prematurity and low birth weight but some effects such as cerebral palsy are likely to be linked to the increased rate of multiple births after ART. Many of the neonatal complications after ART are most likely linked to parental subfertility and are less an effect of the ART technology. The possibility exists that imprinting errors, associated with subfertility and/or ART, may result in long-term morbidity.

Maternal hypothyroidism in early pregnancy and infant structural congenital malformations.

Background. The question is debated on whether maternal hypothyroidism or use of thyroxin in early pregnancy affects the risk for infant congenital malformations. Objectives. To expand the previously published study on maternal thyroxin use in early pregnancy and the risk for congenital malformations. Methods. Data from the Swedish Medical Birth Register were used for the years 1996-2011 and infant malformations were identified from national health registers. Women with preexisting diabetes or reporting the use of thyreostatics, anticonvulsants, or antihypertensives were excluded from analysis. Risk estimates were made as odds ratios (ORs) or risk ratios (RRs) after adjustment for year of delivery, maternal age, parity, smoking, and body mass index. Results. Among 23 259 infants whose mothers in early pregnancy used thyroxin, 730 had a major malformation; among all 1 567 736 infants, 48012 had such malformations. The adjusted OR was 1.06 (95% CI 0.98-1.14). For anal atresia the RR was 1.85 (95% CI 1.00-1.85) and for choanal atresia 3.14 (95% CI 1.26-6.47). The risk of some other malformations was also increased but statistical significance was not reached. Conclusions. Treated maternal hypothyroidism may be a weak risk factor for infant congenital malformations but an association with a few rare conditions is possible.

Maternal obesity and risk of Down syndrome in the offspring.

OBJECTIVE: The objective of this article is to determine if maternal obesity is associated with an increased risk of Down syndrome in the offspring and whether the risk estimates for trisomy 21 based on combined screening is affected by maternal body mass index (BMI). METHODS: Study group I consisted of a nationwide cohort of 1 568 604 women giving birth; outcome was infants born with Down syndrome [Correction made here after initial online publication.]. Adjustment was made for maternal age. Study group II consisted of 10 224 women undergoing 1st trimester combined screening. Outcome was risk assessment for Down syndrome. All women were divided into six BMI groups, and outcomes were evaluated over the BMI strata with BMI 18.5 to 24.9 as reference and correcting for maternal age. RESULTS: Obese women had an increased risk for giving birth to an infant with Down syndrome compared with normal-weight women, BMI 30 to 34.9 odds ratio (OR) 1.31 [95% confidence interval (CI) 1.10-1.55], BMI 35 to 39.9 OR 1.12 (95% CI 0.82-1.53), BMI ≥ 40 OR 1.56 (95% CI 1.00-2.43). The observed and the expected numbers of women with a risk of Down syndrome >1/300 based on 1st trimester combined screen and maternal age were similar in each BMI group. CONCLUSION: Maternal obesity seems to increase the risk for Down syndrome births. The risk estimate for Down syndrome with 1st trimester combined screening is unaffected by BMI.

Maternal and fetal factors which affect fetometry: use of in vitro fertilization and birth register data.

BACKGROUND: Fetometry dating of gestational age is the gold standard in most developed countries but may have some inborn errors. Dating pregnancies after in vitro fertilization can be used for the evaluation of fetometric studies and for studies of variables which may affect them. METHODS: We compared the actual gestational age of 9543 singleton and 869 twin pregnancies with estimates based on second-trimester fetometry. Mean gestational age, percentage of births classified as preterm, and skewness of the distribution of differences between actual and estimated gestational age were studied. Subanalyses were made of data on singletons for males and females, for infants born to overweight or obese women or to smoking women, for infants judged to be small or large for gestational age, and on twins. RESULTS: In the majority of cases, good agreement was found between actual and estimated gestational age but in singletons there was an excess of positive differences resulting in a moderate over-estimate of the rate of preterm births (8%), more marked for females (11%) than for males (6%) and increased for infants born to overweight (7%) or obese (16%) mothers. Singleton infants born small for gestational age also showed an excess of positive differences (3%). These differences were less marked for twins. CONCLUSIONS: In most IVF pregnancies, routine fetometry correctly predicts gestational age but deviations exist which indicate that ultrasound underestimates the age of fetuses that will be born small for gestational age and when the woman is obese. The differences between actual age and estimates based on fetometry seem to be smaller than those between estimates based on last menstrual period and fetometry.

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.

Neonatal complications after maternal concomitant use of SSRI and other central nervous system active drugs during the second or third trimester of pregnancy.

Drugs acting on the central nervous system (CNS) and given to a pregnant woman during the latter part of pregnancy may affect neonatal morbidity of the infant. Little is known on the combined effects of different categories of such drugs. The redeeming of prescriptions for CNS-active drugs during the second or third trimester of pregnancy was studied by linkage between a register of prescribed drugs and the Swedish Medical Birth Register for the deliveries during 2006-2008 (n = 15,045 live-born infants). Neonatal morbidity was defined as the presence of neonatal diagnoses of respiratory problems, hypoglycemia, convulsions, or other CNS pathologic abnormalities including intraventricular hemorrhage, or low 5-minute Apgar score. The risk of such neonatal morbidity after maternal use of selective serotonin reuptake inhibitors (SSRIs) with or without other CNS-active drugs were evaluated as odds ratios or risk ratios, comparing with unexposed infants or infants only exposed to SSRI drugs. An increased risk for neonatal morbidity was seen for most studied groups of CNS-active drugs when used alone. Benzodiazepines seemed to have a stronger effect than other sedatives/hypnotics. The combination of SSRIs with 1 or more other CNS-active drug groups increased the risk for neonatal morbidity. This was seen for all types of sedatives/hypnotics, which may suggest a confounding by indication. Polypharmacy with CNS-active drugs during the later part of the pregnancy seems to increase the occurrence of neonatal morbidity but difference in nature or strength of underlying psychiatric pathology may confound the findings.

The problem of confounding in studies of the effect of maternal drug use on pregnancy outcome.

In most epidemilogical studies, the problem of confounding adds to the uncertainty in conclusions drawn. This is also true for studies on the effect of maternal drug use on birth defect risks. This paper describes various types of such confounders and discusses methods to identify and adjust for them. Such confounders can be found in maternal characteristics like age, parity, smoking, use of alcohol, and body mass index, subfertility, and previous pregnancies including previous birth of a malformed child, socioeconomy, race/ethnicity, or country of birth. Confounding by concomitant maternal drug use may occur. A geographical or seasonal confounding can exist. In rare instances, infant sex and multiple birth can appear as confounders. The most difficult problem to solve is often confounding by indication. The problem of confounding is less important for congenital malformations than for many other pregnancy outcomes.

Are hypnotic benzodiazepine receptor agonists teratogenic in humans?

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Maternal and child outcome after in vitro fertilization--a review of 25 years of population-based data from Sweden.

OBJECTIVE: To summarize data on deliveries after in vitro fertilization (IVF) performed in Sweden up to 2006. DESIGN: Cohort study of women and children, conceived after IVF, with comparisons of deliveries after IVF before and after 1 April 2001. SETTING: Study based on Swedish health registers. POPULATION: Births registered in the Swedish Medical Birth Register with information on IVF from all IVF clinics in Sweden. METHODS: Results from the second study period are summarized, and outcomes between the two periods are compared. Long-term follow-up is based on data from both periods. MAIN OUTCOME MEASURES: Maternal and perinatal outcomes, long-term sequels. RESULTS: Some maternal pregnancy complications decreased in rate, notably pre-eclampsia and premature rupture of membranes. The rate of multiple births and preterm births decreased dramatically, with a better neonatal outcome, including reduced neonatal mortality. No difference in outcome existed between IVF and intracytoplasmic sperm injection or between the use of fresh and cryopreserved embryos, but children born after blastocyst transfer had a slightly higher risk for preterm birth and congenital malformations than children born after cleavage stage transfer. An increased risk for cerebral palsy, possibly for attention deficit and hyperactivity disorder, for impaired visual acuity and for childhood cancer was noted, but these outcomes were rare also after IVF. An increased risk for asthma was demonstrated. No effect on maternal cancer risk was seen. CONCLUSION: A marked decrease in multiple births was the main reason for better pregnancy and neonatal outcome and may also have a beneficial effect on long-term results, notably cerebral palsy.

School performance at age 16 in children exposed to antiepileptic drugs in utero--a population-based study.

PURPOSE: In order to evaluate long-term effects on neurodevelopment in children born to women with epilepsy during pregnancy we studied the children's school grades at age 16. METHODS: We used the Patient Register, the Medical Birth Register, and a local study at South Hospital, Stockholm, to identify women with epilepsy in Sweden who had given birth between 1973 and 1986. The Swedish School Mark Registry was used to obtain information about school grades from the last year of compulsory school, at age 16. Exposed children were compared to all other children born in Sweden between 1973 and 1986. KEY FINDINGS: Medical records were analyzed for 1,235 children. Six hundred forty-one children had been exposed in utero to antiepileptic drugs (AEDs) in monotherapy, 429 in polytherapy, and 165 to no known AED. Children exposed to polytherapy had an increased risk of not receiving a final grade--odds ratio (OR) 2.99 [95% confidence interval (CI) 2.14-4.17]. Children exposed to monotherapy, mainly carbamazepine or phenytoin, did not have a significantly increased risk of not receiving a final grade-OR 1.19 (95% CI 0.79-1.80). Children born to women with epilepsy had a decreased chance of getting a "pass with excellence." SIGNIFICANCE: Exposure to several AEDs in utero may have negative effects on neurodevelopment, and polytherapy should, if possible, be avoided in pregnant women.

Cancer risk in children and young adults conceived by in vitro fertilization.

OBJECTIVES: Studies conducted so far have found no statistically significant increased risk for cancer among children who are born after in vitro fertilization (IVF). METHODS: We followed 26,692 children who were born after IVF during the years 1982-2005 by using the Swedish Cancer Register and compared the number of children who had cancer and were born after IVF with children who were not conceived by IVF. Adjustment was made for year of birth. RESULTS: Maternal age, parity, smoking, subfertility, previous miscarriages, BMI, and multiple births did not significantly affect cancer risk in offspring. High birth weight, premature delivery, and the presence of respiratory diagnoses and low Apgar score were risk factors for cancer. We identified 53 cases of cancer in children who were born after IVF against 38 expected cases: 18 of them with hematologic cancer (15 of them acute lymphoblastic leukemia), 17 with eye or central nervous system tumors, and 12 with other solid cancers. There were 6 cases of Langerhans histiocytosis against 1.0 expected. The total cancer risk estimate was 1.42 (95% confidence interval: 1.09-1.87). CONCLUSIONS: We found a moderately increased risk for cancer in children who were conceived by IVF. Putative intermediary factors could be preterm birth and neonatal asphyxia.

Confirmed association between neonatal phototherapy or neonatal icterus and risk of childhood asthma.

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.

Ocular malformations or poor visual acuity in children born after in vitro fertilization in Sweden.

PURPOSE: To follow up children born after in vitro fertilization (IVF) with respect to eye malformations and poor visual acuity. DESIGN: Observational cohort study based on Swedish health registers. METHODS: Congenital eye malformations were studied in 32 091 children born from 1982 through 2007 and severe visual impairment was studied in 24 628 children born from 1985 through 2005 after IVF in Sweden. Comparisons were made with all children born in Sweden during corresponding periods with adjustment for various confounders. The main outcome measure was the presence of a congenital eye malformation and poor visual acuity. RESULTS: Thirty-six (1.1 per 1000) IVF infants with ocular malformations were identified, and the risk, compared with non-IVF children, was not increased when adjusted for maternal age, parity, smoking, and body mass index (odds ratio, 1.05; 95% confidence interval, 0.75 to 1.47). Severe visual impairment was identified in 25 cases (1.0 per 1000), and the risk increase was statistically significant (odds ratio, 1.65; 95% confidence interval, 1.12 to 2.45) and was only slightly reduced when adjustment as above was made (odds ratio, 1.55; 95% confidence interval, 1.04 to 2.32). When adjustment was made for known length of unwanted childlessness, the OR decreased to 1.15 (95% confidence interval, 0.61 to 2.16). Only 3 of the 25 children with visual impairment had ocular malformations. CONCLUSIONS: Although there is an increased risk for visual impairment among children born after IVF, the individual risk is small and may be secondary to parental characteristics. No increased risk for eye malformations was found.

Blastocyst versus cleavage stage transfer in in vitro fertilization: differences in neonatal outcome?

OBJECTIVE: To compare neonatal outcome of blastocyst and cleavage stage embryo transfers after IVF. DESIGN: Register study. SETTING: Births recorded in the Swedish Medical Birth Register after IVF performed, 2002-2006. PATIENT(S): Treatments reported from all Swedish IVF clinics. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): 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). RESULT(S): 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. CONCLUSION(S): 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.