Placental size at gestational week 36: Comparisons between ongoing pregnancies and deliveries.

INTRODUCTION: We aimed to compare placental size and placental size relative to fetal size (ratio) in ongoing pregnancies examined by magnetic resonance imaging (MRI) at gestational week 36 with placental size among all deliveries at gestational week 36 during the same time period. MATERIAL AND METHODS: Ongoing unselected singleton pregnancies (n = 89) were examined by MRI at median gestational week 36+5 days during 2017-2018, and placental and fetal volumes (cm3 ) were calculated. The placental size and ratio in ongoing pregnancies were compared with placental size and ratio among all deliveries in Norway at gestational week 36 (median gestational week 36+4 days) during 2016-2019 (n = 5582). For comparison of size, we converted volume (cm3 ) in ongoing pregnancies into grams as: cm3 × 1.05 (density of placental and fetal tissue). RESULTS: In ongoing pregnancies, median placental size was 873 (interquartile range [IQR] 265) grams and median size of all delivered placentas was 613 (IQR 290) grams. Placental size was smaller among the delivered placentas independent of delivery mode: 760 (IQR 387) grams among elective cesarean deliveries (n = 465) and 590 (IQR 189) grams among vaginal deliveries after spontaneous onset of labor (n = 2478). Median ratio in ongoing pregnancies was higher than among deliveries: 0.31 (IQR 0.08) vs 0.21 (IQR 0.08). The ratio was higher in ongoing pregnancies independent of delivery mode: 0.24 (IQR 0.17) among elective cesarean deliveries vs 0.21 (IQR 0.05) among vaginal deliveries after spontaneous onset of labor. CONCLUSIONS: The placenta is larger in ongoing pregnancies than among deliveries. This finding suggests that placental size decreases during labor and delivery, possibly by transfer of blood to the fetus. Our finding also suggests that reference values of placental size based on delivered placentas are not valid for ongoing pregnancies.

Is the increasing prevalence of labor induction accompanied by changes in pregnancy outcomes? An observational study of all singleton births at gestational weeks 37-42 in Norway during 1999-2019.

INTRODUCTION: Induction of labor is often performed to prevent adverse perinatal and maternal outcomes, and has become increasingly common. We studied whether changes in prevalence of labor induction in gestational weeks 37-42 weeks were accompanied by changes in adverse pregnancy outcomes or mode of delivery. MATERIAL AND METHODS: We used data from the Medical Birth Registry of Norway, and included all singleton births in gestational weeks 37-42 in Norway, 1999-2019 (n = 1 127 945). We calculated the prevalence of labor induction and outcome measures according to year of birth. We repeated these calculations for each gestational week at birth. RESULTS: The prevalence of labor induction increased from 9.7% to 25.9%, and the increase was particularly high in gestational week 41. A modest decline in fetal deaths was observed in all gestational weeks, except gestational week 41. The overall decline was from 0.18% in 1999-2004 to 0.13% during 2015-2019. There were no overall changes in other perinatal outcomes. The prevalence of postpartum hemorrhage ≥500 ml increased from 11.4% in 1999 to 30.1% in 2019, and operative deliveries increased slightly. The prevalence of acute cesarean section increased from 6.5% to 9.3%, whereas vacuum and/or forceps assisted deliveries increased from 7.8% to 10.4%. CONCLUSIONS: A high increase in labor inductions was accompanied by a modest decline in fetal deaths, but no decline in other adverse perinatal outcomes. In settings where the prevalence of adverse perinatal outcomes is low, the beneficial effect of increased use of labor induction may not outweigh the side effects or the costs.

Har svangerskapsavbrudd betydning for nedgangen i antall fødsler?

BACKGROUND: Birth rates in Norway are declining, and fewer women are having more than two children. Pregnancy termination may impact birth rates. We aimed to study the distribution of pregnancies in Norway according to parity, and whether the proportions of pregnancies ending in termination has changed. MATERIAL AND METHOD: We retrieved figures for pregnancies in Norway during the period 2008-20, based on number of births in the Medical Birth Registry and number of pregnancy terminations in the Registry of Pregnancy Termination. We calculated the proportion of pregnancies resulting in termination according to parity and year. RESULTS: The sum of births and pregnancy terminations fell by 16.4 % during the study period. The absolute decline was most pronounced among nulliparous women, from 34 647 in 2008 to 28 606 in 2020 (17.4 % decline). Of these, the proportion of pregnancies that resulted in a pregnancy termination fell from 25.2 % to 20.5 %. The proportion of pregnancy terminations among women with two, three, four or more previous births was 26.1 %, 34.6 % and 28.2 % in 2008, and 26.1 %, 34.0 % and 29.1 % in 2020, respectively. INTERPRETATION: Both the number of births and the number of pregnancy terminations in Norway fell during the period 2008-20, in all parity groups. The decline was most pronounced in nulliparous women. The number of pregnancy terminations fell more than the number of births. Pregnancy terminations can therefore not explain the decline in birth rates in Norway.

The relation of number of childbirths with age at natural menopause: a population study of 310 147 women in Norway.

STUDY QUESTION: Does age at natural menopause increase with increasing of number of childbirths? SUMMARY ANSWER: Age at menopause increased with increasing number of childbirths up to three childbirths; however, we found no further increase in age at menopause beyond three childbirths. WHAT IS KNOWN ALREADY: Pregnancies interrupt ovulation, and a high number of pregnancies have therefore been assumed to delay menopause. Previous studies have had insufficient statistical power to study women with a high number of childbirths. Thus, the shape of the association of number of childbirths with age at menopause remains unknown. STUDY DESIGN, SIZE, DURATION: A retrospective population study of 310 147 women in Norway who were 50-69 years old at data collection. PARTICIPANTS/MATERIALS, SETTING, METHODS: The data were obtained by two self-administered questionnaires completed by women attending BreastScreen Norway, a population-based screening program for breast cancer. The associations of number of childbirths with age at menopause were estimated as hazard ratios by applying Cox proportional hazard models, adjusting for the woman's year of birth, cigarette smoking, educational level, country of birth, oral contraceptive use and body mass index. MAIN RESULTS AND THE ROLE OF CHANCE: Women with three childbirths had the highest mean age at menopause (51.36 years; 95% CI: 51.33-51.40 years), and women with no childbirths had the lowest (50.55 years; 95% CI: 50.48-50.62 years). Thus, women with no childbirths had higher hazard ratio of reaching menopause compared to women with three childbirths (reference group) (adjusted hazard ratio, 1.24; 95% CI: 1.22-1.27). Beyond three childbirths, we estimated no further increase in age at menopause. These findings were confirmed in sub-analyses among (i) women who had never used hormonal intrauterine device and/or systemic menopausal hormonal therapy; (ii) women who were born before 1950 and (iii) women who were born in 1950 or after. LIMITATIONS, REASONS FOR CAUTION: Information about age at menopause was based on self-reports. WIDER IMPLICATIONS OF THE FINDINGS: If pregnancies truly delay menopause, one would expect that women with the highest number of childbirths had the highest age at menopause. Our results question the assumption that interrupted ovulation during pregnancy delays menopause. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the South-Eastern Norway Regional Health Authority [2016112 to M.S.G.] and by the Norwegian Cancer Society [6863294-2015 to E.K.B.]. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Prevalence of antibodies against SARS-CoV-2 among pregnant women in Norway during the period December 2019 through December 2020.

We studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence among pregnant women in Norway by including all women who were first trimester pregnant (n = 6520), each month from December 2019 through December 2020, in the catchment region of Norway's second-largest hospital. We used sera that had been frozen stored after compulsory testing for syphilis antibodies in antenatal care. The sera were analysed with the Elecsys® Anti-SARS-CoV-2 immunoassay (Roche Diagnostics, Cobas e801). This immunoassay detects IgG/IgM against SARS-CoV-2 nucleocapsid antigen. Sera with equivocal or positive test results were retested with the Liaison® SARS-CoV-2 S1/S2 IgG (DiaSorin), which detects IgG against the spike (S)1 and S2 protein on the SARS-CoV-2 virus. In total, 98 women (adjusted prevalence 1.7%) had SARS CoV-2 antibodies. The adjusted seroprevalence increased from 0.3% (1/445) in December 2019 to 5.7% (21/418) in December 2020. Out of the 98 seropositive women, 36 (36.7%) had serological signs of current SARS-CoV-2 infection at the time of serum sampling, and the incidence remained low during the study period. This study suggests that SARS CoV-2 was present in the first half of December 2019, 6 weeks before the first case was recognised in Norway. The low occurrence of SARS-CoV-2 infection during 2020, may be explained by high compliance to extensive preventive measures implemented early in the epidemic.

The impact of the introduction of intrapartum fetal ECG ST segment analysis. A population study.

INTRODUCTION: ST segment analysis (STAN) of the fetal electrocardiogram was introduced as an adjunct to cardiotocography for intrapartum fetal monitoring 30 years ago. We examined the impact of the introduction of STAN on changes in the occurrence of fetal and neonatal deaths, Apgar scores of <7 at 5 min, intrapartum cesarean sections, and instrumental vaginal deliveries while controlling for time- and hospital-specific trends and maternal risk factors. MATERIAL AND METHODS: Data were retrieved from the Medical Birth Registry of Norway from 1985 to 2014. Individual data were linked to the Education Registry and the Central Person Registry. The study sample included 1 132 022 singleton births with a gestational age of 36 weeks or beyond. Information about the year of STAN introduction was collected from every birth unit in Norway using a questionnaire. Our data structure consisted of a hospital-year panel. We applied a linear probability model with hospital-fixed effects and with adjustment for potentially confounding factors. The prevalence of the outcomes before and after the introduction of STAN were compared within each birth unit. RESULTS: In total, 23 birth units, representing 76% of all births in Norway, had introduced the STAN technology. During the study period, stillbirths declined from 2.6 to 1.9 per 1000 births, neonatal deaths declined from 1.7 to 0.7 per 1000 live births, babies with Apgar score <7 at 5 min after birth increased from 7.4 to 9.5 per 1000 births, intrapartum cesarean sections increased from 6.4% to 9.5%, and instrumental vaginal deliveries increased from 7.8% to 10.9%. Our analyses found that the introduction of STAN was not associated with the decline in proportion of stillbirths (p =0.76) and neonatal deaths (p =0.76) or with the increase in intrapartum cesarean sections (p =0.92) and instrumental vaginal deliveries (p =0.78). However, it was associated with the increased occurrence of Apgar score <7 at 5 min (p =0.01). CONCLUSIONS: There is no evidence that the introduction of STAN contributed to changes in the rates of stillbirths, neonatal deaths, intrapartum cesarean sections, or instrumental vaginal deliveries. There was an association between the introduction of STAN and a small increase in neonates with low Apgar scores.

Offspring birthweight and placental weight-does the type of maternal diabetes matter? A population-based study of 319 076 pregnancies.

INTRODUCTION: Our aim was to estimate the difference in birthweight and in placental weight in pregnancies with type 1 diabetes, type 2 diabetes, and gestational diabetes compared with pregnancies without diabetes. MATERIAL AND METHODS: By using data from the Medical Birth Registry of Norway during the years 2009-2017, we included 319 076 singleton pregnancies with delivery after the 21st week of pregnancy. We used linear regression analyses to estimate the difference in birthweight and in placental weight in grams (g) in pregnancies with type 1 diabetes, type 2 diabetes, and gestational diabetes, using pregnancies without diabetes as the reference. Adjustments were made for pregnancy duration and pre-pregnancy body mass index. RESULTS: In pregnancies without diabetes, mean crude birthweight was 3527 g (SD 552 g). The adjusted mean birthweight was 525 g (95% CI 502-548 g) higher in pregnancies with type 1 diabetes compared with pregnancies without diabetes. In pregnancies with type 2 diabetes, and pregnancies with gestational diabetes, birthweights were 192 g (95% CI 160-223 g) and 102 g (95% CI 93-110 g) higher, respectively. Mean crude placental weight was 664 g (SD 147 g) in pregnancies without diabetes. Compared with pregnancies without diabetes, the adjusted mean placental weight was 109 g (95% CI 101-116 g) higher in pregnancies with type 1 diabetes, 50 g (95% CI 39-60 g) higher in pregnancies with type 2 diabetes, and 31 g (95% CI 28-34 g) higher in pregnancies with gestational diabetes. CONCLUSIONS: The increase in birthweight and in placental weight associated with maternal diabetes was most pronounced for type 1 diabetes, followed by type 2 diabetes, and gestational diabetes.

Placental volume in gestational week 27 measured by three-dimensional ultrasound and magnetic resonance imaging.

INTRODUCTION: Ultrasound is the diagnostic tool of choice in pregnancy. We lack valid ultrasound methods for placental size measurements. Our aim was therefore to compare three-dimensional (3D) ultrasound with magnetic resonance imaging (MRI) for measurements of placental volume. MATERIAL AND METHODS: We measured placental volume by 3D ultrasound and MRI in 100 unselected pregnancies at 27 weeks of gestation (25+4 -28+4  weeks). The 3D ultrasound acquisitions were analyzed offline, and the placental outline was manually traced using the virtual organ computer-aided analysis (VOCAL) 30° rotational technique. The MRI examinations included a T2-weighted gradient echo sequence in the sagittal plane, with 5-mm slices through the entire uterus. The placental outline was manually traced in each slice. The correlation between 3D ultrasound and MRI placental volumes was estimated by intraclass correlation coefficients. Bland-Altman analysis was applied to visualize systematic bias and limits of agreement, in which the ratio MRI placental volume/3D ultrasound placental volume was plotted against the average of the two methods. RESULTS: The intraclass correlation coefficient between 3D ultrasound and MRI measurements was 0.49 (95% confidence interval 0.33-0.63). In general, 3D ultrasound measured smaller placental volumes (median 373 cm3 , interquartile range 309-434 cm3 ) than MRI (median 507 cm3 , interquartile range 429-595 cm3 ) and the systematic bias was 1.44. The 95% limits of agreement between the two methods were wide (0.68-2.21). CONCLUSIONS: We found poor to moderate correlation between 3D ultrasound and MRI placental volume measurements. Generally, 3D ultrasound measured smaller placental volumes than MRI, suggesting that 3D ultrasound failed to visualize the entire placenta. Our findings may hopefully contribute to the improvement of ultrasound methods for placental measurements.

External validation of prognostic models predicting pre-eclampsia: individual participant data meta-analysis.

BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-eclampsia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-eclampsia using individual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting. METHODS: IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-eclampsia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-eclampsia as an outcome were included for validation. We reported the model predictive performance as discrimination (C-statistic), calibration (calibration plots, calibration slope, calibration-in-the-large), and net benefit. Performance measures were estimated separately in each available study and then, where possible, combined across studies in a random-effects meta-analysis. RESULTS: Of 131 published models, 67 provided the full model equation and 24 could be validated in 11 UK cohorts. Most of the models showed modest discrimination with summary C-statistics between 0.6 and 0.7. The calibration of the predicted compared to observed risk was generally poor for most models with observed calibration slopes less than 1, indicating that predictions were generally too extreme, although confidence intervals were wide. There was large between-study heterogeneity in each model's calibration-in-the-large, suggesting poor calibration of the predicted overall risk across populations. In a subset of models, the net benefit of using the models to inform clinical decisions appeared small and limited to probability thresholds between 5 and 7%. CONCLUSIONS: The evaluated models had modest predictive performance, with key limitations such as poor calibration (likely due to overfitting in the original development datasets), substantial heterogeneity, and small net benefit across settings. The evidence to support the use of these prediction models for pre-eclampsia in clinical decision-making is limited. Any models that we could not validate should be examined in terms of their predictive performance, net benefit, and heterogeneity across multiple UK settings before consideration for use in practice. TRIAL REGISTRATION: PROSPERO ID: CRD42015029349 .

Offspring birthweight and placental weight in immigrant women from conflict-zone countries; does length of residence in the host country matter? A population study in Norway.

INTRODUCTION: We aimed to estimate differences in offspring birthweight and placental weight between Norwegian women and immigrants in Norway from countries with armed conflicts. We also studied whether length of residence in Norway was associated with offspring birthweight and placental weight. MATERIAL AND METHODS: We included in our study all singleton births in Norway at gestational week 28 or beyond during the years 1999-2014, to mothers who were born in Somalia, Afghanistan, Iraq (total immigrants n = 18 817), or Norway (n = 668 439). Data were obtained from The Medical Birth Registry of Norway and the Central Person Registry of Norway. We estimated the differences between Norwegian and immigrant women in mean offspring birthweight and mean placental weight by applying linear regression analyses. Adjustments were made for maternal age, parity, year of delivery, gestational age at delivery, preeclampsia, and diabetes. RESULTS: The immigrant women had 206 g (95% CI 199 to 213 g) lower mean offspring birthweight and 16 g (95% CI 14 to 18 g) lower mean placental weight than Norwegian women. Immigrant women with ≥5 years of residence in Norway had higher offspring birthweight (40 g) and higher placental weight (17 g) than immigrant women with <5 years of residence. CONCLUSIONS: Immigrant mothers from Somalia, Afghanistan, and Iraq gave birth to infants and placentas with lower weight than Norwegian women. However, the difference between Norwegian women and immigrant women was reduced by length of residence in Norway.

Childbirth close to natural menopause: does age at menopause matter?

RESEARCH QUESTION: Does a successful spontaneous pregnancy in the years close to natural menopause depend on age at menopause? DESIGN: This was a retrospective population-based study of 4157 parous postmenopausal women in Norway, born during the years 1925-1940. Data were obtained by two self-administered questionnaires in the HUNT2 Survey (1995-1997). We calculated the proportions of women who gave birth within 5 years and within 10 years prior to menopause both among all women, and according to categories of age at menopause. RESULTS: Overall, 2.7% (114/4157) of all women gave birth within 5 years, and 11.7% (487/4157) gave birth within 10 years, prior to menopause. Among women with menopause before the age of 45 years, 23.5% (81/344) gave birth within 5 years, and 55.5% (191/344) gave birth within 10 years, before menopause. Among the women with menopause at the age of 55 years or older, no women (0/474) gave birth within 5 years, and 0.2% (1/474) gave birth within 10 years, prior to menopause. CONCLUSIONS: More than half of the women with menopause before the age of 45 years gave birth within the 10 years before natural menopause, whereas virtually no women with menopause at the age of 55 years or older did. Thus, the length of the sterile interval before natural menopause may vary by age at menopause.

Menopausal hormone therapy and breast cancer risk: effect modification by body mass through life.

It is not known whether increased breast cancer risk caused by menopausal hormone therapy (HT) depends on body mass patterns through life. In a prospective study of 483,241 Norwegian women aged 50-69 years at baseline, 7656 women developed breast cancer during follow-up (2006-2013). We combined baseline information on recalled body mass in childhood/adolescence and current (baseline) body mass index (BMI) to construct mutually exclusive life-course body mass patterns. We assessed associations of current HT use with breast cancer risk according to baseline BMI and life-course patterns of body mass, and estimated relative excess risk due to interaction (RERI). Within all levels of baseline BMI, HT use was associated with increased risk. Considering life-course body mass patterns as a single exposure, we used women who "remained at normal weight" through life as the reference, and found that being "overweight as young" was associated with lower risk (hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.76-0.94), whereas women who "gained weight" had higher risk (HR 1.20, 95% CI 1.12-1.28). Compared to never users of HT who were "overweight as young", HT users who either "remained at normal weight" or "gained weight" in adulthood were at higher risk than expected when adding the separate risks (RERI 0.52, 95% CI 0.09-0.95, and RERI 0.37, 95% CI - 0.07-0.80), suggesting effect modification. Thus, we found that women who remain at normal weight or gain weight in adulthood may be more susceptible to the risk increasing effect of HT compared to women who were overweight as young.

Maternal concentrations of human chorionic gonadotrophin in very early IVF pregnancies and duration of pregnancy: a follow-up study.

RESEARCH QUESTION: Are maternal concentrations of human chorionic gonadotropin (HCG) on a fixed day after embryo transfer associated with duration of pregnancy? DESIGN: A follow-up study of 1917 singleton pregnancies after IVF was performed. Embryos were cultured for 2 days and maternal HCG concentration quantified on day 12 after embryo transfer. Duration of pregnancy was obtained from the Medical Birth Registry of Norway. Association of HCG concentration (log2-transformed) with duration of pregnancy was estimated as hazard ratios (HR) with 95% confidence intervals (CI) by applying Cox regression proportional hazard models, where time to delivery for pregnancies shortened because of planned Caesarean delivery or induction of labour was treated as censored. RESULTS: The estimated median duration of pregnancy from embryo transfer was 266 days (95% CI 266-267 days). Maternal concentration of HCG on day 12 after embryo transfer varied from 1 to 588 IU/l (median 117 IU/l). Duration of pregnancy decreased by increasing HCG concentration, significantly in pregnancies delivered at full term ((257-270 days after embryo transfer; HR 1.127, 95% CI 1.026-1.238, P = 0.012). For each doubling of HCG concentration on day 12 after embryo transfer, duration of pregnancy was shortened by 0.51 days. Adjustment for maternal age, prepregnancy body mass index, being a first-time mother and number of embryos transferred did not change the association. CONCLUSION: High maternal HCG concentration on a fixed day after embryo transfer is likely to indicate early embryo implantation. After embryo transfer, pregnancies with early implantation are shorter than pregnancies with late implantation.

Exercise in pregnancy: an association with placental weight?

BACKGROUND: Women with high levels of physical exercise have an increased demand for oxygen and nutrients. Thus, in pregnancies of women with high levels of exercise, it is conceivable that the supply of oxygen and nutrients to the placenta is suboptimal, and growth could be impaired. OBJECTIVE: The objective was to study the association of frequency of exercise during pregnancy with placental weight and placental to birthweight ratio. STUDY DESIGN: This was a prospective study of 80,515 singleton pregnancies in the Norwegian Mother and Child Cohort Study. Frequency of exercise was self-reported by a questionnaire at pregnancy weeks 17 and 30. Information on placental weight and birthweight was obtained by linkage to the Medical Birth Registry of Norway. RESULTS: Placental weight decreased with increasing frequency of exercise (tests for trend, P < .001). For nonexercisers in pregnancy week 17, the crude mean placental weight was 686.1 g compared with 667.3 g in women exercising ≥6 times weekly (difference, 18.8 g; 95% confidence interval, 12.0-25.5). Likewise, in nonexercisers in pregnancy week 30, crude mean placental weight was 684.9 g compared with 661.6 g in women exercising ≥6 times weekly (difference, 23.3 g; 95% confidence interval, 14.9-31.6). The largest difference in crude mean placental weight was seen between nonexercisers at both time points and women exercising ≥6 times weekly at both time points (difference, 31.7 g; 95% confidence interval, 19.2-44.2). Frequency of exercise was not associated with placental to birthweight ratio. CONCLUSION: We found decreasing placental weight with increasing frequency of exercise in pregnancy. The difference in placental weight between nonexercisers and women with exercising ≥6 times weekly was small and may have no clinical implications.

Saving Newborn Babies - The Benefits of Interventions in Neonatal Care in Norway over More Than 40 Years.

The aim of this study was to examine the effect that the introduction of new medical interventions at birth has had on mortality among newborn babies in Norway during the period 1967-2011. During this period, there has been a significant decline in mortality, in particular for low birth weight infants. We identified four interventions that together explained about 50% of the decline in early neonatal and infant mortality: ventilators, antenatal steroids, surfactant and insure. The analyses were performed on a large set of data, encompassing more than 1.6 million deliveries (Medical Birth Registry of Norway). The richness of the data allowed us to perform several robustness tests. Our study indicates that the introduction of new medical interventions has been a very important channel through which the decline in mortality among newborn babies occurred during the second half of the last century. Copyright © 2016 John Wiley & Sons, Ltd.

Vitamin D-binding protein and 25-hydroxyvitamin D during pregnancy in mothers whose children later developed type 1 diabetes.

BACKGROUND: Levels of 25-hydroxyvitamin D (25-OH D) during late pregnancy have been linked to type 1 diabetes risk in the offspring. Vitamin D-binding protein increases in concentration during pregnancy. We aimed to test whether concentrations of vitamin D-binding protein and 25-OH D throughout pregnancy differed between women whose offspring later developed type 1 diabetes (cases) and controls. METHODS: A nested case-control study was conducted within a cohort of pregnant women from all over Norway in 1992-1994. Offspring registered in The Norwegian Childhood Diabetes Registry, diagnosed with type 1 diabetes before age 15, defined the case women, giving 113 cases in the study. Two hundred twenty controls were randomly selected within the same cohort. One to four serum samples from each participant drawn at different time points during pregnancy were analysed for vitamin D-binding protein and 25-OH D by radioimmunoassay. RESULTS: Vitamin D-binding protein and 25-OH D significantly increased by gestational week (p < 0.001) and tended to be lower in cases than in controls, -0.27 µmol/L (95% CI -0.57, 0.03) and -5.01 nmol/L (95% CI -8.03, -0.73), respectively. While first and second trimester concentrations of vitamin D-binding protein and 25-OH D alone were not significantly different, lower third trimester concentrations tended to be associated with higher risk of type 1 diabetes in the offspring, albeit at borderline significance after mutual adjustment. CONCLUSIONS: In this first study of maternal vitamin D-binding protein measured throughout pregnancy and risk of type 1 diabetes in offspring, lower concentration, particularly in the third trimester, tended to be associated with type 1 diabetes. Copyright © 2016 John Wiley & Sons, Ltd.

The associations of maternal body mass index with birthweight and placental weight. Does maternal diabetes matter? A population study of 106 191 pregnancies.

INTRODUCTION: The aim of this study was to study whether the associations of maternal body mass index with offspring birthweight and placental weight differ by maternal diabetes status. MATERIAL AND METHODS: We performed a population study of 106 191 singleton pregnancies by using data from the years 2009-2012 in the Medical Birth Registry of Norway. We estimated changes in birthweight and in placental weight (in grams) by maternal body mass index by linear regression analysis. RESULTS: In pregnancies of women without diabetes, birthweight increased by 14.7 g (95% confidence interval 14.1-15.2) per unit increase in maternal body mass index, and the increase in placental weight was 4.2 g (95% confidence interval 4.0-4.4). In pregnancies of women with gestational diabetes, the corresponding figures were 11.8 g (95% confidence interval 8.3-15.4) and 2.9 g (95% confidence interval 1.7-4.0). In pregnancies of women with type 1 diabetes we found no significant changes in birthweight or in placental weight by maternal body mass index. Overall, mean birthweight was 513.9 g (95% confidence interval 475.6-552.1) higher in pregnancies involving type 1 diabetes than in pregnancies of women without diabetes. Mean placental weight was 102.1 g (95% confidence interval 89.3-114.9) higher. Also, in pregnancies of women with gestational diabetes, both birthweight and placental weight were higher than in women without diabetes (168.2 g and 46.5 g, respectively). Adjustments were made for maternal body mass index and gestational age at birth. CONCLUSIONS: Birthweight and placental weight increased with increasing maternal body mass index in pregnancies of women without diabetes and in pregnancies of women with gestational diabetes, but not in pregnancies of women with type 1 diabetes. Independent of body mass index, mean birthweight and mean placental weight were highest in pregnancies of women with type 1 diabetes.

Intrauterine fetal death and risk of shoulder dystocia at delivery.

INTRODUCTION: Vaginal delivery is recommended after intrauterine fetal death. However, little is known about the risk of shoulder dystocia in these deliveries. We studied whether intrauterine fetal death increases the risk of shoulder dystocia at delivery. MATERIAL AND METHODS: In this population-based register study using the Medical Birth Registry of Norway, we included all singleton pregnancies with vaginal delivery of offspring in cephalic presentation in Norway during the period 1967-2012 (n = 2 266 118). Risk of shoulder dystocia was estimated as absolute risk (%) and odds ratio with 95% confidence interval. Adjustment was made for offspring birthweight (in grams). We performed sub-analyses within categories of birthweight (<4000 and ≥4000 g) and in pregnancies with maternal diabetes. RESULTS: Shoulder dystocia occurred in 1.1% of pregnancies with intrauterine fetal death and in 0.8% of pregnancies without intrauterine fetal death (p < 0.0001) (crude odds ratio 1.5, 95% confidence interval 1.2-4.9). After adjustment for birthweight, the odds ratio was 5.9 (95% confidence interval 4.7-7.4). In pregnancies with birthweight ≥4000 g, shoulder dystocia occurred in 14.6% of pregnancies with intrauterine fetal death and in 2.8% of pregnancies without intrauterine fetal death (p < 0.001) (crude odds ratio 5.9, 95% confidence interval 4.5-7.9). In pregnancies with birthweight ≥4000 g and concurrent maternal diabetes, shoulder dystocia occurred in 57.1% of pregnancies with intrauterine fetal death and 9.6% of pregnancies without intrauterine fetal death (p < 0.001) (crude odds ratio 12.6, 95% confidence interval 5.9-26.9). CONCLUSIONS: Intrauterine fetal death increased the risk of shoulder dystocia at delivery, and the absolute risk of shoulder dystocia was particularly high if offspring birthweight was high and the mother had diabetes.