Mette Bliddal

Maternal Pre-Pregnancy BMI and Intelligence Quotient (IQ) in 5-Year-Old Children: A Cohort Based Study

BACKGROUND An association between maternal pre-pregnancy BMI and childhood intelligence quotient (IQ) has repeatedly been found but it is unknown if this association is causal or due to confounding caused by genetic or social factors. METHODS We used a cohort of 1,783 mothers and their 5-year-old children sampled from the Danish National Birth Cohort. The children participated between 2003 and 2008 in a neuropsychological assessment of cognitive ability including IQ tests taken by both the mother and the child. Linear regression analyses were used to estimate the associations between parental BMI and child IQ adjusted for a comprehensive set of potential confounders. Child IQ was assessed with the Wechsler Primary and Preschool Scales of Intelligence--Revised (WPPSI-R). RESULTS The crude association between maternal BMI and child IQ showed that BMI was adversely associated with child IQ with a reduction in IQ of -0.40 point for each one unit increase in BMI. This association was attenuated after adjustment for social factors and maternal IQ to a value of -0.27 (-0.50 to -0.03). After mutual adjustment for the fathers BMI and all other factors except maternal IQ, the association between paternal BMI and child IQ yielded a regression coefficient of -0.26 (-0.59 to 0.07), which was comparable to that seen for maternal BMI (-0.20 (-0.44 to 0.04)). CONCLUSION Although maternal pre-pregnancy BMI was inversely associated with the IQ of her child, the similar association with paternal BMI suggests that it is not a specific pregnancy related adiposity effect.

Mental disorders in motherhood according to prepregnancy BMI and pregnancy-related weight changes—A Danish cohort study

BACKGROUND Previous studies have shown an association between prepregnancy BMI and postpartum depression, but little is known about this association beyond one year postpartum and the influence of postpartum weight retention (PPWR). METHODS We used data from 70355 mothers from the Danish National Birth Cohort to estimate the associations between maternal prepregnancy BMI and PPWR, respectively, and incident depression/anxiety disorders until six years postpartum. Outcome was depression or anxiety diagnosed clinically or filling a prescription for an antidepressant. Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Follow-up started at the day of delivery. For the analysis regarding PPWR, follow-up started six months postpartum. RESULTS Underweight, overweight and obesity were associated with depression and/or anxiety disorders when compared to normal-weight, though the associations were attenuated after adjustments (HR 1.24 [95% CI 1.06-1.45], 1.05 [95% CI 0.96-1.15] and 1.07 [95% CI 0.95-1.21] for underweight, overweight and obese, respectively). Compared to mothers who had returned to their prepregnancy BMI, risk of depression/anxiety disorders was increased for mothers, who from prepregnancy to 6 months postpartum experienced either weight loss >1 BMI unit (HR 1.19 [95% CI 1.06-1.25]), weight gain of 2-3 BMI units (HR 1.23 [95% CI 1.08-1.40]), or weight gain of ≥3 BMI units (HR 1.21 [95% CI 1.05-1.40]). LIMITATION Causal direction and mechanisms behind the associations are largely unknown. CONCLUSIONS Low prepregnancy body weight and postpartum weight gain or loss are associated with occurrence of depression and anxiety disorders.

Association of Pre-Pregnancy Body Mass Index, Pregnancy-Related Weight Changes, and Parity With the Risk of Developing Degenerative Musculoskeletal Conditions.

To examine how pre‐pregnancy body mass index (BMI), parity, and pregnancy‐related weight changes are associated with long‐term risk of degenerative musculoskeletal conditions.

Examining Non-Participation to the Maternal Follow-up Within the Danish National Birth Cohort

A follow-up questionnaire on maternal health was distributed within the Danish National Birth Cohort (established in 1996-2002) 14 years after the index birth. Responses were obtained from 41,466 (53.2%) of 78,010 eligible mothers. To ensure the appropriate use of these data, the possibility of selection bias due to nonparticipation had to be evaluated. We estimated 4 selected exposure-outcome associations (prepregnancy weight-depression; exercise-degenerative musculoskeletal conditions; smoking-heart disease; and alcohol consumption-breast cancer). We adjusted for several factors associated with participation and applied inverse probability weighting. To estimate the degree of selection bias, we calculated relative odds ratios for the relationship between the baseline cohort and the subset participating in the Maternal Follow-up. Participating women were generally healthier, of higher social status, and older than the baseline cohort. However, selection bias in the chosen scenarios was limited; ratios of the odds ratios ranged from -14% to 5% after adjustment for age, parity, social status, and, if the variable was not the exposure variable, prepregnancy body mass index, exercise, smoking, and alcohol consumption. Applying inverse probability weighting did not further reduce bias. In conclusion, while participants differed somewhat from the baseline cohort, selection bias was limited after factors associated with participation status were accounted for.

Depressive symptoms in women's midlife in relation to their body weight before, during and after childbearing years.

This study aimed to examine how weight and weight changes related to pregnancy were associated with depressive symptoms 11–16 years after childbirth.

Breastfeeding and later maternal risk of hypertension and cardiovascular disease – The role of overall and abdominal obesity

In this study, we examined how any, full, and partial breastfeeding durations were associated with maternal risk of hypertension and cardiovascular disease (CVD), and how prepregnancy body mass index (BMI) and waist circumference 7 years postpartum influenced these associations. A total of 63,260 women with live-born singleton infants in the Danish National Birth Cohort (1996-2002) were included. Interviews during pregnancy and 6 and 18 months postpartum provided information on prepregnancy weight, height, and the duration of full and partial breastfeeding. Waist circumference was self-reported 7 years postpartum. Cox regression models were used to estimate hazard ratios of incident hypertension and CVD, registered in the National Patient Register from either 18 months or 7 years postpartum through 15 years postpartum. Any breastfeeding ≥4 months was associated with 20-30% lower risks of hypertension and CVD compared to <4 months in both normal/underweight and overweight/obese women. At follow-up starting 7 years postpartum, similar risk reductions were observed after accounting for waist circumference adjusted for BMI. Partial breastfeeding >2 months compared to ≤2 months, following up to 6 months of full breastfeeding, was associated with 10-25% lower risk of hypertension and CVD. Compared with short breastfeeding duration, additional partial breastfeeding was as important as additional full breastfeeding in reducing risk of hypertension and CVD. Altogether, longer duration of breastfeeding was associated with lower maternal risk of hypertension and CVD irrespective of prepregnancy BMI and abdominal adiposity 7 years after delivery. Both full and partial breastfeeding contributed to an improved cardiovascular health in mothers.

PS4:86 Obstetric and neonatal outcomes in systemic lupus erythematosus: a population-based register study

Introduction In women with systemic lupus erythematosus (SLE) pregnancies may be negatively affected by disease activity and medical treatment. Increased frequencies of adverse outcome including preterm delivery and perinatal morbidity/mortality have been reported. However, different frequencies are reported from different studies. Aim and hypothesis Utilising national health registers we want to investigate maternal and fetal outcomes in Danish pregnant SLE patients compared to outcomes in the background population. Methods The outcome of pregnancies in Danish SLE patients in 1997–2016 is studied utilising healthcare-registries (the Danish National Patient Registry (NPR) and the Medical Birth Register (MBR)) and trends are described. Study population and material: All females with a diagnosis of SLE in the study period are identified from the NPR (ICD-8 and ICD-10 diagnoses of SLE). The outcome of all pregnancies (routinely registered in NPR and MBR) is compared to the outcome in an age-matched cohort of pregnant women without SLE (each SLE patient is matched with 20 females from the background population). Data about infants are retrieved from the MBR Statistics: Using logistic regression we will examine if risk of adverse maternal and fetal outcome is higher in women with SLE than in women without SLE, by calculating crude and adjusted odds ratios Results Frequencies of adverse maternal outcomes including preeclampsia, preterm delivery and Caesarean section, and adverse infant outcome including asphyxia, growth retardation and low Apgar score will be presented. Crude and adjusted odds ratios will be calculated comparing pregnancies in SLE females with pregnancies of non-SLE females. Data are at present being retrieved from the Danish authorities and subsequent data analysis is expected to be completed December 2017. Approximately 800 women with SLE are expected to be included in the study.

Epidemiology of cutaneous lupus erythematosus and the associated risk of systemic lupus erythematosus: a nationwide cohort study in Denmark:

Objectives The objectives of this paper are to describe the epidemiology of cutaneous lupus erythematosus (CLE) and its subtypes in Denmark, and to investigate the probability of receiving a subsequent diagnosis of systemic lupus erythematosus (SLE) and the related time course. Methods A nationwide registry-based cohort study was conducted in Denmark based on data from the Danish National Patient Registry from 1998 to 2013 using International Classification of Diseases, Revision 10. Results We identified 2380 patients with CLE. The annual incidence rate (IR) of CLE was 2.74/100,000 with a female:male ratio of 4:1. During 12,047 person-years of follow-up, 8% were diagnosed with SLE. The probability of receiving a subsequent diagnosis of SLE was 12.9% after 10 years taking death as a competing risk into consideration, and the probability was highest among women and patients diagnosed with subacute CLE. The median time until a diagnosis of SLE was 2.05 years. Conclusions This is the first nationwide study on CLE in Denmark. Although we found the annual IR of CLE and the risk of receiving an additional diagnosis of SLE to be lower than previously described, continued monitoring and thorough information for patients with CLE is important due to the inherent risk of SLE.

A New Fracture Risk Assessment Tool (FREM) Based on Public Health Registries

Some conditions are already known to be associated with an increased risk of osteoporotic fractures. Other conditions may also be significant indicators of increased risk. The aim of the current study was to identify conditions for inclusion in a fracture prediction model (fracture risk evaluation model [FREM]) for automated case finding of high‐risk individuals of hip or major osteoporotic fractures (MOFs). We included the total population of Denmark aged 45+ years (N = 2,495,339). All hospital diagnoses from 1998 to 2012 were used as possible conditions; the primary outcome was MOFs during 2013. Our cohort was split randomly 50/50 into a development and a validation dataset for deriving and validating the predictive model. We applied backward selection on ICD‐10 codes (International Classification of Diseases and Related Health Problems, 10th Revision) by logistic regression to develop an age‐adjusted and sex‐stratified model. The FREM for MOFs included 38 and 43 risk factors for women and men, respectively. Testing FREM for MOFs in the validation cohort showed good accuracy; it produced receiver‐operating characteristic (ROC) curves with an area under the ROC curve (AUC) of 0.750 (95% CI, 0.741 to 0.795) and 0.752 (95% CI, 0.743 to 0.761) for women and men, respectively. The FREM for hip fractures included 32 risk factors for both genders and showed an even higher accuracy in the validation cohort as AUCs of 0.874 (95% CI, 0.869 to 0.879) and 0.851 (95% CI, 0.841 to 0.861) for women and men were found, respectively. We have developed and tested a prediction model (FREM) for identifying men and women at high risk of MOFs or hip fractures by using solely existing administrative data. The FREM could be employed either at the point of care integrated into electronic patient record systems to alert physicians or deployed centrally in a national case‐finding strategy where patients at high fracture risk could be invited to a focused DXA program.

Reproductive life in women with celiac disease; a nationwide, population-based matched cohort study

STUDY QUESTION How does celiac disease (CD) influence womens reproductive life, both prior to and after the diagnosis? SUMMARY ANSWER Prior to the diagnosis of CD, an increased risk of adverse pregnancy outcomes was seen, whereas after the diagnosis, no influence on reproductive outcomes was found. WHAT IS KNOWN ALREADY CD has been associated with several conditions influencing female reproduction and pregnancy outcomes including spontaneous abortion and stillbirth. STUDY DESIGN, SIZE, DURATION A nationwide matched cohort study following 6319 women diagnosed with CD and 63166 comparison women and identifying reproductive events between the ages of 15 and 50 years. PARTICIPANTS/MATERIALS, SETTING, METHODS Through linkage of several Danish national health registers, we identified all women diagnosed with CD between 1977 and 2016. We identified an age- and sex-matched comparison cohort and obtained data on reproductive outcomes for both cohorts. Adjusted stratified Cox and logistic regression models were used to estimate differences in reproductive outcomes between women with and without CD. MAIN RESULTS AND THE ROLE OF CHANCE Comparing women with diagnosed CD with the non-CD women, the chance of pregnancy, live birth and risk of stillbirth, molar and ectopic pregnancy, spontaneous abortion and abortion due to foetal disease was the same. However, prior to being diagnosed, CD women had an excess risk of spontaneous abortion equal to 11 extra spontaneous abortions per 1000 pregnancies (adjusted odds ratio (OR) = 1.12, 95% CI: 1.03, 1.22) and 1.62 extra stillbirths per 1000 pregnancies (adjusted OR = 1.57, 95% CI: 1.05, 2.33) compared with the non-CD women. In the period 0-2 years prior to diagnosis fewer pregnancies occurred in the undiagnosed CD group, equal to 25 (95% CI: 20-31) fewer pregnancies per 1000 pregnancies compared to the non-CD group and in addition, fewer undiagnosed CD women initiated ART-treatment in this period, corresponding to 4.8 (95% CI: 0.9, 8.7) fewer per 1000 women compared to non-CD women. LIMITATIONS, REASONS FOR CAUTION Validity of the diagnoses in the registers was not confirmed, but reporting to the registers is mandatory for all hospitals in Denmark. Not all spontaneous abortions will come to attention and be registered, whereas live- and stillbirths, ectopic and molar pregnancies and abortion due to foetal disease are unlikely not to be registered. We adjusted for several confounding factors but residual confounding cannot be ruled out. WIDER IMPLICATIONS OF THE FINDINGS These findings suggest that undiagnosed CD can affect female reproduction and the focus should be on early detection of CD in risk groups. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the Health Research Fund of Central Denmark Region and The Hede Nielsens Foundation, Denmark. The authors report no conflicts of interest in this work.