Lipid levels after childbirth and association with number of children: A population-based cohort study.

OBJECTIVE: Low parity women are at increased risk of cardiovascular mortality. Unfavourable lipid profiles have been found in one-child mothers years before they conceive. However, it remains unclear whether unfavourable lipid profiles are evident in these women also after their first birth. The aim was to estimate post-pregnancy lipid levels in one-child mothers compared to mothers with two or more children and to assess these lipid's associations with number of children. METHODS: We used data on 32 618 parous women (4 490 one-child mothers and 28 128 women with ≥2 children) examined after first childbirth as part of Cohort of Norway (1994-2003) with linked data on reproduction and number of children from the Medical Birth Registry of Norway (1967-2008). Odds ratios (ORs) with 95% confidence intervals (CIs) for one lifetime pregnancy (vs. ≥2 pregnancies) by lipid quintiles were obtained by logistic regression and adjusted for age at examination, year of first birth, body mass index, oral contraceptive use, smoking and educational level. RESULTS: Compared to women with the lowest quintiles, ORs for one lifetime pregnancy for the highest quintiles of LDL and total cholesterol were 1.30 (95%CI: 1.14-1.45) and 1.43 (95%CI: 1.27-1.61), respectively. Sensitivity analysis (women <40 years) showed no appreciable change in our results. In stratified analyses, estimates were slightly stronger in overweight/obese, physically inactive and women with self-perceived bad health. CONCLUSIONS: Mean lipid levels measured after childbirth in women with one child were significantly higher compared to mothers with two or more children and were associated with higher probability of having only one child. These findings corroborate an association between serum lipid levels and one lifetime pregnancy (as a feature of subfecundity), emphasizing that these particular women may be a specific predetermined risk group for cardiovascular related disease and death.

Perinatal death and exposure to dental amalgam fillings during pregnancy in the population-based MoBa cohort.

OBJECTIVES: The aim was to gain knowledge regarding the risk of perinatal death related to exposure to dental amalgam fillings in the mother. DESIGN: Population-based observational cohort study. SETTING: The Norwegian Mother and Child Cohort Study, a Norwegian birth cohort of children born in 1999-2008 conducted by the Norwegian Institute of Public Health. PARTICIPANTS: 72,038 pregnant women with data on the number of teeth filled with dental amalgam. MAIN OUTCOME MEASURES: Data on perinatal death (stillbirth ≥ 22 weeks plus early neonatal death 0-7 days after birth) were obtained from the Medical Birth Registry of Norway. RESULTS: The absolute risk of perinatal death ranged from 0.20% in women with no amalgam-filled teeth to 0.67% in women with 13 or more teeth filled with amalgam. Analyses including the number of teeth filled with amalgam as a continuous variable indicated an increased risk of perinatal death by increasing number of teeth filled with dental amalgam (crude OR 1.065, 95% CI 1.034 to 1.098, p<0.001). After adjustment for potential confounders (mothers' age, education, body mass index, parity, smoking during pregnancy, alcohol consumption during pregnancy) included as categorical variables, there was still an increased risk for perinatal death associated with increasing number of teeth filled with amalgam (ORadj 1.041, 95% CI 1.008 to 1.076, p = 0.015). By an increased exposure from 0 to 16 teeth filled with amalgam, the model predicted an almost doubled odds ratio (ORadj 1.915, 95% CI 1.12 to 3.28). In groups with 1 to 12 teeth filled with amalgam the adjusted odds ratios were slightly, but not significantly, increased. The group with the highest exposure (participants with 13 or more teeth filled with amalgam) had an adjusted OR of 2.34 (95% CI 1.27 to 4.32; p = 0.007). CONCLUSION: The current findings suggest that the risk of perinatal death could increase in a dose-dependent way based on the mother's number of teeth filled with dental amalgam. However, we cannot exclude that the relatively modest odds ratios could be a result of residual confounding. Additional studies on the relationship between exposure to dental amalgam fillings during pregnancy and perinatal death are warranted.

Women's prepregnancy lipid levels and number of children: a Norwegian prospective population-based cohort study.

OBJECTIVE: To study prepregnancy serum lipid levels and the association with the number of children. DESIGN: Prospective, population-based cohort. SETTING: Linked data from the Cohort of Norway and the Medical Birth Registry of Norway. PARTICIPANTS: 2645 women giving birth to their first child during 1994-2003 (488 one-child mothers and 2157 women with ≥2 births) and 1677 nulliparous women. MAIN OUTCOME MEASURES: ORs for no and one lifetime pregnancy (relative to ≥2 pregnancies) obtained by multinomial logistic regression, adjusted for age at examination, education, body mass index (BMI), smoking, time since last meal and oral contraceptive use. RESULTS: Assessed in quintiles, higher prepregnant triglyceride (TG) and TG to high-density lipoprotein (TG:HDL-c) ratio levels were associated with increased risk of one lifetime pregnancy compared with having ≥2 children. Compared with the highest quintile, women in the lowest quintile of HDL cholesterol levels had an increased risk of one lifetime pregnancy (OR 1.7, 95% CI 1.2 to 2.4), as were women with the highest low-density lipoprotein (LDL) cholesterol, TG and TG:HDL-c ratio quintiles (compared with the lowest) (OR 1.2, 95% CI 0.8 to 1.7; OR 2.2, 95% CI 1.5 to 3.2; and OR 2.2, 95% CI 1.5 to 3.2, respectively). Similar effects were found in women with BMI≥25 and the highest LDL and total cholesterol levels in risk of lifetime nulliparity. CONCLUSION: Women with unfavourable prepregnant lipid profile had higher risk of having no or only one child. These findings substantiate an association between prepregnant serum lipid levels and number of children. Previously observed associations between low parity and increased cardiovascular mortality may in part be due to pre-existing cardiovascular disease lipid risk factors.

Season of Conception, Smoking, and Preeclampsia in Norway.

BACKGROUND: Preeclampsia (PE) is a dangerous and unpredictable pregnancy complication. A seasonal pattern of risk would suggest that there are potentially preventable environmental contributors, but prior analyses have not adjusted for confounding by PE risk factors that are associated with season of conception. METHODS: Seasonal effects were modeled and tested by representing each day of the year as an angle on a unit circle and using trigonometric functions of those angles in predictive models, using "harmonic analysis." We applied harmonic Cox regression to model confounder-adjusted effects of the estimated day of the year of conception on risk of PE for births from the Medical Birth Registry of Norway for deliveries between 1999 and 2009. We also examined effect measure modification by parity, latitude (region), fetal sex, and smoking. RESULTS: In adjusted models, PE risk was related to season, with higher risk in spring conceptions and lower risk in autumn conceptions, with a risk amplitude (maximum compared with minimum) of about 20%. The pattern replicated across subpopulations defined by parity, latitude (region), fetal sex, and smoking. CONCLUSIONS: These results suggest that there is a seasonal driver for PE, with effects that are not modified by parity, latitude, fetal sex, or smoking. https://doi.org/10.1289/EHP963.

Chronic Hypertension in Women after Perinatal Exposure to Preeclampsia, Being Born Small for Gestational Age or Preterm.

BACKGROUND: There is an established association between adverse events during perinatal life and chronic hypertension in adult life. However, disadvantageous conditions often co-exist in the same pregnancy. We investigated single and joint perinatal exposure to preeclampsia, being born small for gestational age (SGA) or preterm and subsequent risk of chronic hypertension. METHODS: The study population consisted of 731 008 primiparous women from Norway and Sweden registered in the Medical Birth Registers, both as infants and as first time mothers between 1967-2009 (Norway) and 1973-2010 (Sweden). Risk of chronic hypertension in early pregnancy was calculated in women with perinatal exposures to preeclampsia, born SGA or preterm by log-binominal regression analysis, and adjusted for maternal age and level of education in the first generation. RESULTS: The rate of chronic hypertension was 0.4%. Risk of chronic hypertension was associated with single perinatal exposure to preeclampsia, being born SGA or preterm with adjusted relative risk (95% confidence interval, CI) of 2.2 (95% CI 1.8, 2.7), 1.1 (95% CI 1.0, 1.3), and 1.3 (95% CI 1.0, 1.5) respectively. The risks increased after joint exposures, with an almost fourfold risk increase after perinatal exposure to preeclampsia and preterm birth. Additional adjustment for BMI and smoking in the second generation in a subset of the cohort only had a minor impact on the results. CONCLUSIONS: Perinatal exposure to preeclampsia, being born SGA or preterm is independently associated with increased risk of chronic hypertension. The highest risk was seen after exposure to preeclampsia, especially if combined with SGA or preterm birth.

Maternal Smoking Status in Successive Pregnancies and Risk of Having a Small for Gestational Age Infant.

BACKGROUND: Smoking during pregnancy is linked to having a small for gestational age (SGA) baby. We estimated SGA risk among women who smoked persistently, quit smoking or started smoking during their first two pregnancies. METHODS: Data from the population-based Medical Birth Registry of Norway was used to evaluate self-reported smoking at the beginning and end of two successive pregnancies among 118 355 Nordic women giving birth 1999-2014. Relative risks (RR) with 95% confidence intervals (CI) of SGA in the second pregnancy were estimated using adjusted generalised linear models with non-smokers during both pregnancies serving as referent category. RESULTS: Daily smokers throughout both pregnancies had almost threefold increased SGA risk in the second pregnancy (RR 2.9, 95% CI 2.7, 3.1). Daily smokers in the first pregnancy, who abstained in the second, had a 1.3-fold increased risk (95% CI 1.1, 1.5). Intermediate risks were found among persistent daily smokers who quit by the end of the second pregnancy (RR 2.0, 95% CI 1.6, 2.4) and non-smokers in first pregnancy who smoked daily throughout their second (RR 1.8, 95% CI 1.4, 2.3). Persistently smoking women without SGA in first pregnancy, had a 2.7-fold increased risk of SGA in second pregnancy (95% CI 2.5, 3.0). CONCLUSIONS: Smoking throughout two successive pregnancies was associated with the greatest increased SGA risk compared with non-smokers, while cessation before or during the second pregnancy reduced this risk. Women who smoked in the first pregnancy without experiencing SGA are not protected against SGA in second pregnancy if they continue smoking.

Risk factors for recurrence of hypertensive disorders of pregnancy, a population-based cohort study.

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) tend to recur from one pregnancy to the next. The aims of the study were to assess the recurrence risk according to type of HDP defined by gestational age at birth and to examine whether recurrence is associated with the following additional risk factors for HDP: maternal age, smoking, inter-delivery interval, diabetes, body mass index, and fetal growth restriction, and to assess temporal trends in these associations. MATERIAL AND METHODS: All women with two singleton births in the Medical Birth Registry of Norway 1967-2012 (n = 742 980) were included in this population-based cohort study. Logistic regression was used to calculate odds ratios for the risk of recurrent HDP according to type of HDP. RESULTS: The highest odds ratio of recurrence was observed for the same type of HDP based on gestational age at delivery. After gestational hypertension and term preeclampsia, the risk for the same type to recur increased 10-fold, whereas after late and early preterm preeclampsia, the risk increased 27- and 97-fold, respectively. The recurrence of early preterm preeclampsia was less influenced by additional risk factors compared with term HDP. Recurrence of early preterm HDP was significantly lower from 1993 onwards. CONCLUSIONS: Recurrent HDP tended to be of the same type as the previous HDP. Risk of recurrence associated with additional risk factors was observed particularly after term. The odds ratio of recurrence of early preterm HDP was significantly lower from 1993 onwards.

Prenatal exposure to dental amalgam and pregnancy outcome.

OBJECTIVE: Questions have been raised about potential risks of prenatal exposure to mercury from amalgam fillings during pregnancy. The aim of this study was to assess possible associations between exposure to amalgam fillings in pregnant women participating in a large cohort study and adverse pregnancy outcome. METHODS: In the Norwegian Mother and Child Cohort Study (MoBa), a valid information about the number of teeth with amalgam fillings and dental treatment, including new amalgam fillings placed or removed during pregnancy, was available from 69 474 pregnancies. The information was obtained from two questionnaires sent to the women at 17 and 30 weeks of pregnancy, and the data were linked to the Medical Birth Registry of Norway. Logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (95% CI) as a measure of association between pregnancy outcome and prenatal exposure to amalgam fillings. RESULTS: Logistic regression models, including mothers' age, education, BMI, parity, smoking during pregnancy, and alcohol consumption during pregnancy revealed no significant associations between the number of teeth with amalgam fillings and early preterm delivery, late preterm delivery, low birthweight, malformation or stillbirth. CONCLUSIONS: We found no evidence for serious perinatal consequences of maternal exposure to amalgam fillings during pregnancy.

Season and preterm birth in Norway: A cautionary tale.

BACKGROUND: Preterm birth is a common, costly and dangerous pregnancy complication. Seasonality of risk would suggest modifiable causes. METHODS: We examine seasonal effects on preterm birth, using data from the Medical Birth Registry of Norway (2,321,652 births), and show that results based on births are misleading and a fetuses-at-risk approach is essential. In our harmonic-regression Cox proportional hazards model we consider fetal risk of birth between 22 and 37 completed weeks of gestation. We examine effects of both day of year of conception (for early effects) and day of ongoing gestation (for seasonal effects on labour onset) as modifiers of gestational-age-based risk. RESULTS: Naïve analysis of preterm rates across days of birth shows compelling evidence for seasonality (P < 10(-152)). However, the reconstructed numbers of conceptions also vary with season (P < 10(-307)), confounding results by inducing seasonal variation in the age distribution of the fetal population at risk. When we instead properly treat fetuses as the individuals at risk, restrict analysis to pregnancies with relatively accurate ultrasound-based assessment of gestational age (available since 1998) and adjust for socio-demographic factors and maternal smoking, we find modest effects of both time of year of conception and time of year at risk, with peaks for early preterm near early January and early July. CONCLUSIONS: Analyses of seasonal effects on preterm birth are demonstrably vulnerable to confounding by seasonality of conception, measurement error in conception dating, and socio-demographic factors. The seasonal variation based on fetuses reveals two peaks for early preterm, coinciding with New Year's Day and the early July beginning of Norway's summer break, and may simply reflect a holiday-related pattern of unintended conception.

An international contrast of rates of placental abruption: an age-period-cohort analysis.

BACKGROUND: Although rare, placental abruption is implicated in disproportionately high rates of perinatal morbidity and mortality. Understanding geographic and temporal variations may provide insights into possible amenable factors of abruption. We examined abruption frequencies by maternal age, delivery year, and maternal birth cohorts over three decades across seven countries. METHODS: Women that delivered in the US (n = 863,879; 1979-10), Canada (4 provinces, n = 5,407,463; 1982-11), Sweden (n = 3,266,742; 1978-10), Denmark (n = 1,773,895; 1978-08), Norway (n = 1,780,271, 1978-09), Finland (n = 1,411,867; 1987-10), and Spain (n = 6,151,508; 1999-12) were analyzed. Abruption diagnosis was based on ICD coding. Rates were modeled using Poisson regression within the framework of an age-period-cohort analysis, and multi-level models to examine the contribution of smoking in four countries. RESULTS: Abruption rates varied across the seven countries (3-10 per 1000), Maternal age showed a consistent J-shaped pattern with increased rates at the extremes of the age distribution. In comparison to births in 2000, births after 2000 in European countries had lower abruption rates; in the US there was an increase in rate up to 2000 and a plateau thereafter. No birth cohort effects were evident. Changes in smoking prevalence partially explained the period effect in the US (P = 0.01) and Sweden (P<0.01). CONCLUSIONS: There is a strong maternal age effect on abruption. While the abruption rate has plateaued since 2000 in the US, all other countries show declining rates. These findings suggest considerable variation in abruption frequencies across countries; differences in the distribution of risk factors, especially smoking, may help guide policy to reduce abruption rates.

Change in paternity, risk of placental abruption and confounding by birth interval: a population-based prospective cohort study in Norway, 1967-2009.

OBJECTIVES: We examined abruption risk in relation to change in paternity, and evaluated if birth interval confounds this association. SETTING: Population-based study of singleton births in Norway between 1967 and 2009. PARTICIPANTS: Women who had their first two (n=747 566) singleton births in the Norwegian Medical Birth Registry. The associations between partner change between pregnancies and birth interval were examined in relation to abruption in a series of logistic regression models. PRIMARY OUTCOME MEASURES: Risk, as well as unadjusted and adjusted OR of placental abruption in relation to change in paternity and interval between births. RESULTS: Among women without abruption in their first pregnancy, the risks of abruption in the second pregnancy were 4.7 and 6.5 per 1000 in women who had the same and different partners, respectively (OR=1.39, 95% CI 1.26 to 1.53). After adjustments for confounders including birth interval and smoking, partner change was not associated with abruption (OR=1.01, 95% CI 0.79 to 1.32). Among women with abruption in the first pregnancy, the association between partner change and abruption in the second pregnancy was 0.98 (95% CI 0.75 to 1.28). Interval <1 year was associated with increased abruption risk in the second pregnancy among women with the same as well as different partners, but interval over 4 years was only associated with increased risk among women with the same partner. No such patterns were seen for recurrent abruption. CONCLUSIONS: We find no evidence that a change in partner is associated with increased abruption risk. Theories supporting an immune maladaptation hypothesis afforded by change in paternity are not supported insofar as abruption is concerned.

Can 'early programming' be partly explained by smoking? Results from a prospective, population-based cohort study.

BACKGROUND: Numerous studies have focused the association between low birthweight and later disease. Our objective was to study the association between birthweight and later adult smoking and thereby explore a possible mechanism for the association between low birthweight and later adult disease. METHODS: We studied associations between birthweight of women (n=247704) born in 1967-1995 and smoking habits at the end of their pregnancy 13-42 years later in a prospective, population-based cohort study from The Medical Birth Registry of Norway. Similarly, the association between birthweight of men (n=194393) and smoking habits of their partners were assessed. Finally, we studied the relation between smoking habits of the participating women and the cause specific death of their mothers (n=222808). RESULTS: Twenty per cent of women with birthweight less than 2000 g were adult daily smokers compared with 11% with birthweight 4000-4499 g [relative risk=1.8, 95% confidence interval 1.4, 2.2]. Similarly, we found an association between men's birthweight and their partners smoking habits. Mothers of smoking women had doubled risk of dying from lung cancer and from cardiovascular disease compared with mothers of non-smoking women. CONCLUSIONS: Being born with low birthweight is associated with smoking in adulthood. Associations of adult smoking with partners' birthweight and mothers' smoking-related causes of death suggest a shared smoking environment, and may account for some of the established association between birthweight and later cardiovascular disease.

Cancer in children and young adults born after assisted reproductive technology: a Nordic cohort study from the Committee of Nordic ART and Safety (CoNARTaS).

STUDY QUESTION: Do children and young adults born after assisted reproductive technology (ART) have an increased risk of cancer? SUMMARY ANSWER: Children born after ART showed no overall increase in the rate of cancer when compared with children born as a result of spontaneous conception. WHAT IS KNOWN ALREADY: Children born after ART have more adverse perinatal outcomes, i.e. preterm births, low birthweights and birth defects. Previous studies have shown divergent results regarding the risk of cancer among children born after ART. STUDY DESIGN, SIZE, DURATION: A retrospective Nordic population-based cohort study was performed, comprising all children born after ART in Sweden, Denmark, Finland and Norway between 1982 and 2007. The mean (±standard deviation) follow-up time was 9.5 (4.8) years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Children born after ART (n = 91 796) were compared with a control group of children born after spontaneous conception. This control group was almost 4-fold the size of the ART group (n = 358 419) and matched for parity, year of birth and country. Data on perinatal outcomes and cancer were obtained from the National Medical Birth Registries, the Cancer Registries, the Patient Registries and the Cause of Death Registries. The cancer diagnoses were divided into 12 main groups. Hazard ratios (HRs) and adjusted HR were calculated. Adjustments were carried out for country, maternal age, parity, sex, gestational age and birth defects. MAIN RESULTS AND THE ROLE OF CHANCE: There was no significant increase in overall cancer rates among children born after ART when compared with children born after spontaneous conception (adjusted HR 1.08; 95% CI 0.91-1.27). Cancer, of any form, was found among 181 children born after ART (2.0/1000 children, 21.0/100 000 person-years) compared with 638 children born after spontaneous conception (1.8/1000 children, 18.8/100 000 person-years). Leukaemia was the most common type of cancer (n = 278, 0.62/1000 children) but no significantly increased incidence was found among children born after ART. An increased risk was observed for 2 of 12 cancer groups. They were central nervous system tumours (adjusted HR 1.44; 95% CI 1.01-2.05) and malignant epithelial neoplasms (adjusted HR 2.03; 95% CI 1.06-3.89); the absolute risks were 0.46/1000 and 0.15/1000 children, respectively, corresponding to an absolute increased risk of 0.14/1000 and 0.08/1000 children, respectively. LIMITATIONS, REASONS FOR CAUTION: As this is an observational study, the main limitation is the fact that it is not possible to adjust for all potential confounders. We were not able to control for confounders such as socio-economic status and perinatal factors, such as Apgar score, which other studies have suggested affect cancer rates. WIDER IMPLICATIONS OF THE FINDINGS: The results of this large population-based cohort study are in agreement with most previously published studies. The main findings are reassuring for couples undergoing ART, children born after ART and clinicians working with ART. STUDY FUNDING/COMPETING INTERESTS: No conflict of interest was reported. The study was supported by grants from The European Society for Human Reproduction and Embryology (ESHRE), Sahlgrenska University Hospital, Gothenburg, Sweden, the University of Copenhagen, Denmark, the Danish Agency of Science, Technology and Innovation and the Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).

Perinatal mortality by gestational week and size at birth in singleton pregnancies at and beyond term: a nationwide population-based cohort study.

BACKGROUND: Whether gestational age per se increases perinatal mortality in post-term pregnancy is unclear. We aimed at assessing gestational week specific perinatal mortality in small-for-gestational-age (SGA) and non-SGA term and post-term gestations, and specifically to evaluate whether the relation between post-term gestation and perinatal mortality differed before and after ultrasound was introduced as the standard method of gestational age estimation. METHODS: A population-based cohort study, using data from the Medical Birth Registry of Norway (MBRN), 1967-2006, was designed. Singleton births at 37 through 44 gestational weeks (n = 1 855 682), excluding preeclampsia, diabetes and fetal anomalies, were included. Odds ratios (OR) with 95% confidence intervals (CI) for perinatal mortality and stillbirth in SGA and non-SGA births by gestational week were calculated. RESULTS: SGA infants judged post-term by LMP had significantly higher perinatal mortality than post-term non-SGA infants at 40 weeks, independent of time period (highest during 1999-2006 [OR 9.8, 95% CI: 5.7-17.0]). When comparing years before (1967-1986) versus after (1987-2006) ultrasound was introduced, there was no decrease in the excess mortality for post-term SGA versus non-SGA births (ORs from 6.1 [95% CI: 5.2-7.1] to 6.7 [5.2-8.5]), while mortality at 40 weeks decreased significantly (ORs from 4.6, [4.0-5.3] to 3.2 [2.5-3.9]). When assessing stillbirth risk (1999-2006), more than 40% of SGA stillbirths (11/26) judged to be ≥41 weeks by LMP were shifted to lower gestational ages using ultrasound estimation. CONCLUSIONS: Mortality risk in post-term infants was strongly associated with growth restriction. Such infants may erroneously be judged younger than they are when using ultrasound estimation, so that the routine assessment for fetal wellbeing in the prolonged gestation may be given too late.

Perinatal outcomes of children born after frozen-thawed embryo transfer: a Nordic cohort study from the CoNARTaS group.

STUDY QUESTIONS: What are the risks of adverse outcomes in singletons born after frozen-thawed embryo transfer (FET)? SUMMARY ANSWER: Singletons born after FET have a better perinatal outcome compared with singletons born after fresh IVF and ICSI as regards low birthweight (LBW) and preterm birth (PTB), but a worse perinatal outcome compared with singletons born after spontaneous conception. WHAT IS KNOWN ALREADY: Previous studies have shown a worse perinatal outcome in children born after IVF in general compared with children born after spontaneous conception. In singletons born after FET, a lower rate of PTB and LBW and a higher rate of large for gestational age (LGA) compared with singletons born after fresh IVF have been shown. STUDY DESIGN: A retrospective Nordic population-based cohort study of all singletons conceived after FET in Denmark, Norway and Sweden until December 2007 was performed. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Singletons born after FET (n = 6647) were compared with a control group of singletons born after fresh IVF and ICSI (n = 42 242) and singletons born after spontaneous conception (n = 288 542). Data on perinatal outcomes were obtained by linkage to the national Medical Birth Registries. Odds ratios were calculated for several perinatal outcomes and adjustments were made for maternal age, parity, year of birth, offspring sex and country of origin. MAIN RESULTS AND THE ROLE OF CHANCE: Singletons born after FET had a lower risk of LBW (adjusted odds ratio (aOR) 0.81, 95% confidence interval (CI) 0.71-0.91), PTB (aOR 0.84, 95% CI 0.76-0.92), very PTB (VPTB; aOR 0.79, 95% CI 0.66-0.95) and small for gestational age (SGA; aOR 0.72, 95% CI 0.62-0.83), but a higher risk of post-term birth (aOR 1.40, 95% CI 1.27-1.55), LGA (aOR 1.45, 95% CI 1.27-1.64), macrosomia (aOR 1.58, 95% CI 1.39-1.80) and perinatal mortality (aOR 1.49, 95% CI 1.07-2.07) compared with singletons born after fresh IVF and ICSI. Compared with children conceived after spontaneous conception, singletons born after FET had a higher risk of LBW (aOR 1.27, 95% CI 1.13-1.43), very LBW (aOR 1.69, 95% CI 1.33-2.15), PTB (aOR 1.49, 95% CI 1.35-1.63), VPTB (aOR 2.68, 95% CI 2.24-3.22), SGA (aOR 1.18, 95% CI 1.03-1.35), LGA (aOR 1.29, 95% CI 1.15-1.45), macrosomia (aOR 1.29, 95% CI 1.15-1.45) and perinatal (aOR 1.39, 95% CI 1.03-1.87) neonatal (aOR 1.87, 95% CI 1.23-2.84) and infant mortality (aOR 1.92, 95% CI 1.36-2.72). When analyzing trends over time, the risk of being born LGA increased over time for singletons born after FET compared with singletons born after fresh IVF and ICSI (P = 0.04). LIMITATIONS, REASONS FOR CAUTION: As in all observational studies, the possible role of residual confounding factors and bias should be considered. In this study, we were not able to control for confounding factors, such as BMI, smoking and reason for, or length of, infertility. WIDER IMPLICATIONS OF THE FINDINGS: Perinatal outcomes in this large population-based cohort of children born after FET from three Nordic countries compared with fresh IVF and ICSI and spontaneous conception were in agreement with the literature.

Birth outcomes among offspring of adult cancer survivors: a population-based study.

Do cancer and cancer treatment influence patients' subsequent pregnancies and outcomes for the offspring? In this study, we compared birth outcomes in 3,915 female and male survivors and 144,653 controls from the general population with similar parity, by merging data from the Cancer Registry and the Medical Birth Registry of Norway. The cancer survivors were diagnosed at age 16-45 in the period 1967-2004. Subgroups of nulliparous survivors (childless before cancer) and primiparous (one pregnancy before and one after cancer) were analyzed, using logistic regression to compare birth outcomes with controls, focusing perinatal death, congenital anomalies, preterm birth (<37 gestational weeks) and low birth weight (LBW, <2,500 g). We adjusted for maternal age, birth period and educational level. Nulliparous female survivors' offspring had increased risk of preterm birth (OR = 1.30 [95% CI 1.05-1.61]) but similar risks of LBW and perinatal death as their controls. Primiparous female survivors differed from their controls, with higher frequency of preterm birth (OR = 1.89 [95% CI 1.40-2.56]) and LBW at term (OR = 2.02 [95% CI 1.15-3.55]). A borderline significant increase of perinatal death was seen among offspring of primiparous female survivors, with OR = 1.92 (95% CI 0.98-3.76). Offspring of male survivors did not differ from their controls. For all cancer types combined, no increased risk of congenital anomalies was seen among either female or male survivors' offspring. Pregnant female cancer survivors should be offered close follow-up, as there is an increased risk of adverse birth outcomes, in particular among those with higher parities.

Parent-offspring body mass index associations in the Norwegian Mother and Child Cohort Study: a family-based approach to studying the role of the intrauterine environment in childhood adiposity.

In the present study, the authors investigated the role of the intrauterine environment in childhood adiposity by comparing the maternal-offspring body mass index (BMI) association with the paternal-offspring BMI association when the offspring were 3 years of age, using parental prepregnancy BMI (measured as weight in kilograms divided by height in meters squared). The parent-offspring trios (n = 29,216) were recruited during pregnancy from 2001 to 2008 into the Norwegian Mother and Child Cohort Study conducted by The Norwegian Institute of Public Health. Data from self-administered questionnaires were used in linear regression analyses. Crude analyses showed similar parental-offspring BMI associations; the mean difference in offspring BMI was 0.15 (95% confidence interval: 0.13, 0.16) per each 1-standard-deviation increase in maternal BMI and 0.15 (95% confidence interval: 0.13, 0.17) per each 1-standard-deviation increase in paternal BMI. After all adjustments, the mean difference in offspring BMI per each 1-standard-deviation increment of maternal BMI was 0.12, and the mean difference in offspring BMI per each 1-standard-deviation increment of paternal BMI was 0.13. There was no strong support for heterogeneity between the associations (P > 0.6). In conclusion, results from the present large population-based study showed similar parental-offspring BMI associations when the offspring were 3 years of age, which indicates that the maternal-offspring association may be explained by shared familial (environmental and genetic) risk factors rather than by the intrauterine environment.

Exposure to tobacco smoke in utero and subsequent plasma lipids, ApoB, and CRP among adult women in the MoBa cohort.

BACKGROUND: Recent findings suggest that maternal smoking during pregnancy may play a role in the development of metabolic alterations in offspring during childhood. However, whether such exposure increases the risk of developing similar metabolic alterations during adulthood is uncertain. OBJECTIVE: We evaluated the association of in utero exposure to maternal tobacco smoke with plasma lipids, apolipoprotein B (apoB), and C-reactive protein (CRP) in adulthood. METHODS: The study was based on a subsample of the Norwegian Mother and Child Cohort Study (MoBa) and included 479 pregnant women with plasma lipids, apoB, and CRP measurements. Information on in utero exposure to tobacco smoke, personal smoking, and other factors were obtained from the women by a self-completed questionnaire at enrollment, at approximately 17 weeks of gestation. RESULTS: Women exposed to tobacco smoke in utero had higher triglycerides [10.7% higher; 95% confidence interval (CI): 3.9, 17.9] and lower high-density lipoprotein cholesterol (HDL) (-1.9 mg/dL; 95% CI: -4.3, 0.5) compared with unexposed women, after adjusting for age, physical activity, education, personal smoking, and current body mass index (BMI). Exposed women were also more likely to have triglycerides ≥ 200 mg/dL [adjusted odds ratio (aOR) = 2.5; 95% CI: 1.3, 5.1] and HDL < 50 mg/dL (aOR = 2.3; 95% CI: 1.1, 5.0). Low-density lipoprotein cholesterol, total cholesterol, and apoB were not associated with the exposure. CRP was increased among exposed women; however, after adjustment for BMI, the association was completely attenuated. CONCLUSIONS: In this population, in utero exposure to tobacco smoke was associated with high triglycerides and low HDL in adulthood, 18-44 years after exposure.

Self-reported smoking status and plasma cotinine concentrations among pregnant women in the Norwegian Mother and Child Cohort Study.

INTRODUCTION: Underreporting of smoking in epidemiologic studies is common and may constitute a validity problem, leading to biased association measures. In this prospective study, we validated self-reported tobacco use against nicotine exposure assessed by plasma cotinine in the Norwegian Mother and Child Cohort Study (MoBa). METHODS: The study was based on a subsample of 2,997 women in the MoBa study who delivered infants during the period 2002-2003. Self-reported tobacco use (test variable) and plasma cotinine concentrations (gold standard) were assessed at approximately gestational week 18. RESULTS: Daily smoking was reported by 9% of the women, occasional smoking by 4%, and nonsmoking by 86% of the women. Sensitivity and specificity for self-reported smoking status were calculated using a cotinine cut-off estimated from the study population (30 nmol/l). Plasma cotinine concentrations ≥30 nmol/l were found in 94% of self-reported daily smokers, 66% of occasional smokers, and 2% of nonsmokers. After the numbers of self-reported nonsmokers with cotinine concentrations above the cut-off limit were added, the daily smoking prevalence increased from 9 to 11%. The sensitivity and specificity for self-reported daily smoking, using 30 nmol/l as the cut-off concentration, were 82 and 99%, respectively. DISCUSSION: These findings suggest that self-reported tobacco use is a valid marker for tobacco exposure in the MoBa cohort.

In utero exposure to maternal tobacco smoke and subsequent obesity, hypertension, and gestational diabetes among women in the MoBa cohort.

BACKGROUND: Environmental factors influencing the developmental origins of health and disease need to be identified and investigated. In utero exposure to tobacco smoke has been associated with obesity and a small increase in blood pressure in children; however, whether there is a corresponding increased risk of conditions such as diabetes and hypertension during adulthood remains unclear. OBJECTIVE: Our goal was to assess the association of self-reported in utero exposure to tobacco smoke with the prevalence of obesity, hypertension, type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM) in women 14-47 years of age. METHODS: We conducted a cross-sectional analysis of the Norwegian Mother and Child Cohort Study, which enrolled pregnant women in Norway from 1999 thorough 2008. Exposure to tobacco smoke in utero (yes vs. no) was ascertained on the baseline questionnaire (obtained at ~ 17 weeks' gestation); the outcomes were ascertained from the Medical Birth Registry of Norway and the questionnaire. Our analysis included 74,023 women. RESULTS: Women exposed to tobacco smoke in utero had 1.53 times the odds of obesity [95% confidence interval (CI): 1.45, 1.61] relative to those unexposed, after adjusting for age, education, and personal smoking. After further adjustment for body mass index, the odds ratio for hypertension was 1.68 (95% CI: 1.19, 2.39); for T2DM 1.14 (95% CI: 0.79, 1.65); and for GDM 1.32 (95% CI: 1.10, 1.58) among exposed compared with unexposed. CONCLUSIONS: Exposure to tobacco smoke in utero was associated with obesity, hypertension, and GDM in adult women. The possibility that the associations were attributable to unmeasured confounding cannot be excluded.