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.

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 .

Preeclampsia in pregnancies with and without diabetes: the associations with placental weight. A population study of 655 842 pregnancies.

INTRODUCTION: Women with diabetes are at increased risk of preeclampsia, and women with diabetes tend to deliver placentas and offspring that are large-for-gestational-age. We therefore studied placental weight in preeclamptic pregnancies according to maternal diabetes status. MATERIAL AND METHODS: Information on all singleton births from 1999 through 2010 (n = 655 842) were obtained from the Medical Birth Registry of Norway. We used z-scores of placental weight to adjust for differences in gestational age at birth between deliveries, and compared the distribution of placental weight z-scores, in deciles, in preeclamptic pregnancies with and without diabetes, and in non-preeclamptic pregnancies with and without diabetes. RESULTS: Overall, the prevalence of preeclampsia was higher in pregnancies with diabetes than in pregnancies without diabetes (9.9% vs. 3.6%). Among preeclamptic pregnancies, having a placental weight in the highest decile was nearly three times more frequent (28.8%) in pregnancies with diabetes than in pregnancies without diabetes (9.8%). In the lowest decile, preeclamptic pregnancies with diabetes were underrepresented (7.5%), and preeclamptic pregnancies without diabetes were overrepresented (13.6%). Among pregnancies with preterm delivery, the above patterns were more pronounced, with 30.1% of the placentas in in preeclamptic pregnancies with diabetes in the highest decile, and 19.5% of the placentas in preeclamptic pregnancies without diabetes in the lowest decile. CONCLUSIONS: These results suggest that women with diabetes who develop preeclampsia have a higher placental weight than other women with preeclampsia or non-preeclamptic women.

Recurrence of hypertensive disorders of pregnancy: an individual patient data metaanalysis.

OBJECTIVE: We performed an individual participant data (IPD) metaanalysis to calculate the recurrence risk of hypertensive disorders of pregnancy (HDP) and recurrence of individual hypertensive syndromes. STUDY DESIGN: We performed an electronic literature search for cohort studies that reported on women experiencing HDP and who had a subsequent pregnancy. The principal investigators were contacted and informed of our study; we requested their original study data. The data were merged to form one combined database. The results will be presented as percentages with 95% confidence interval (CI) and odds ratios with 95% CI. RESULTS: Of 94 eligible cohort studies, we obtained IPD of 22 studies, including a total of 99,415 women. Pooled data of 64 studies that used published data (IPD where available) showed a recurrence rate of 18.1% (n=152,213; 95% CI, 17.9-18.3%). In the 22 studies that are included in our IPD, the recurrence rate of a HDP was 20.7% (95% CI, 20.4-20.9%). Recurrence manifested as preeclampsia in 13.8% of the studies (95% CI,13.6-14.1%), gestational hypertension in 8.6% of the studies (95% CI, 8.4-8.8%) and hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome in 0.2% of the studies (95% CI, 0.16-0.25%). The delivery of a small-for-gestational-age child accompanied the recurrent HDP in 3.4% of the studies (95% CI, 3.2-3.6%). Concomitant HELLP syndrome or delivery of a small-for-gestational-age child increased the risk of recurrence of HDP. Recurrence increased with decreasing gestational age at delivery in the index pregnancy. If the HDP recurred, in general it was milder, regarding maximum diastolic blood pressure, proteinuria, the use of oral antihypertensive and anticonvulsive medication, the delivery of a small-for-gestational-age child, premature delivery, and perinatal death. Normotensive women experienced chronic hypertension after pregnancy more often after experiencing recurrence (odds ratio, 3.7; 95% CI, 2.3-6.1). CONCLUSION: Among women that experience hypertension in pregnancy, the recurrence rate in a next pregnancy is relatively low, and the course of disease is milder for most women with recurrent disease. These reassuring data should be used for shared decision-making in women who consider a new pregnancy after a pregnancy that was complicated by hypertension.

Placental weight and placental weight to birthweight ratio in relation to Apgar score at birth: a population study of 522 360 singleton pregnancies.

OBJECTIVE: To study whether placental weight or placental weight to birthweight ratio are associated with Apgar score in the newborn 5 min after birth. DESIGN: Population-based registry study. SETTING: The Medical Birth Registry of Norway. POPULATION: All singleton live births during the period 1999-2008, a total of 522 360 births. METHODS: The placental weight to birthweight ratios were divided into quartiles within 2-week intervals of gestational age at birth, hence 25% of the pregnancies were within each group. We studied the proportion of pregnancies in the highest quartile of placental weight and placental weight to birthweight ratio according to Apgar score 5 min after birth, and estimated the odds ratio for Apgar score ≤7 if the placental weight to birthweight ratio was in the highest quartile, and used the lowest quartile as reference. MAIN OUTCOME MEASURE: Apgar score in the newborn 5 min after birth. RESULTS: In births after pregnancy week 29, and at every 2-week gestational age interval, the mean placental weight and placental weight to birthweight ratio were higher in newborn with Apgar score ≤7 than in infants with Apgar >7. The crude odds ratio of Apgar score ≤7 was 1.65 (95% CI 1.57-1.74), comparing the highest to the lowest quartile of placental weight to birthweight ratio. Adjustments for gestational age, birthweight, infant sex, maternal age, preeclampsia, diabetes and congenital malformations did not alter the odds ratio significantly. CONCLUSIONS: Placental weight and placental weight to birthweight ratio were higher in pregnancies with infant Apgar score ≤7 compared with Apgar score >7.

Maternal age and serum concentration of human chorionic gonadotropin in early pregnancy.

OBJECTIVE: To study whether maternal age is associated with serum concentration of human chorionic gonadotropin in early pregnancy. DESIGN: Cross-sectional study. SETTING: Oslo University Hospital in Oslo, Norway. POPULATION: All vital pregnancies in gestational week 8 conceived by in vitro fertilization between February 1996 and February 2013 (n = 4472). METHODS: Serum concentrations of human chorionic gonadotropin were measured on day 12 after embryo transfer/day 16 following ovulation induction. Trends in geometric means of human chorionic gonadotropin concentrations by maternal age group were tested by linear regression analysis. We also studied the association of maternal age (years) with log-transformed human chorionic gonadotropin concentrations, and adjustments were made for number of embryos transferred, method of in vitro fertilization and year (period) of embryo transfer. MAIN OUTCOME MEASURE: Serum concentration of human chorionic gonadotropin. RESULTS: Geometric mean concentrations of human chorionic gonadotropin decreased with increasing maternal age (p = 0.024, test for trend by weighted linear regression). Also, we estimated a significant negative association of maternal age with log-transformed human chorionic gonadotropin concentrations (adjusted regression coefficient -0.011, standard error 0.003, p < 0.001). CONCLUSIONS: Serum concentrations of human chorionic gonadotropin in very early pregnancy decreased with maternal age. Since human chorionic gonadotropin is synthesized in trophoblast cells only, the lower human chorionic gonadotropin concentrations in women of advanced age may reflect functional impairment or delayed proliferation of trophoblast cells in early pregnancy in these women.

Two-dimensional (2D) placental ultrasound measurements - The correlation with placental volume measured by magnetic resonance imaging (MRI).

INTRODUCTION: Information about placental size in ongoing pregnancies may aid the identification of pregnancies with increased risk of adverse outcome. Placental volume can be measured using magnetic resonance imaging (MRI). However, this method is not universally available in antenatal care. Ultrasound is the diagnostic tool of choice in pregnancy. Therefore, we studied whether simple two-dimensional (2D) ultrasound placental measurements were correlated with placental volume measured by MRI. METHODS: We examined a convenience sample of 104 ongoing pregnancies at gestational week 27, using both ultrasound and MRI. The ultrasound measurements included placental length, width and thickness. Placental volume was measured using MRI. The correlation between each 2D placental ultrasound measurement and placental volume was estimated by applying Pearson's correlation coefficient (r). RESULTS: Mean placental length was 17.2 cm (SD 2.1 cm), mean width was 14.7 cm (SD 2.1 cm), and mean thickness was 3.2 cm (SD 0.6 cm). Mean placental volume was 536 cm3 (SD 137 cm3). The 2D ultrasound measurements showed poor correlation with placental volume (placental length; r = 0.27, width; r = 0.37, and thickness r = 0.13). DISCUSSION: Simple 2D ultrasound measurements of the placenta were poorly correlated with placental volume and cannot be used as proximate measures of placental volume. Our finding may be explained by the large variation between pregnancies in intrauterine placental shape.

Fetal death and placental weight/birthweight ratio: a population study.

OBJECTIVE: To study the association of placental weight and placental weight/birthweight ratio with gestational age-specific fetal death. DESIGN: Population-based study. SETTING: Medical Birth Registry of Norway. POPULATION: All singleton births in Norway, 1999-2008 (n = 534 892). METHODS: Gestational age-specific quartiles of placental weight and placental weight/birthweight ratio were estimated, and proportions of fetal deaths and live births within the lowest and highest quartile were compared. The risk of fetal death associated with placental weight/birthweight ratio was estimated as crude and adjusted odds ratios. MAIN OUTCOME MEASURES: Offspring vital status. RESULTS: Pregnancies with fetal death were overrepresented in the lowest quartile of placental weight and placental weight/birthweight ratio in term and preterm deliveries. In preterm deliveries, fetal deaths were also overrepresented in the highest placental weight/birthweight ratio. Adjusted odds ratio of fetal death in preterm deliveries was 1.67 (95% confidence interval 1.44-1.94) for placental weight/birthweight ratio in the lowest quartile and 1.79 (95% confidence interval 1.55-2.08) in the highest quartile. Corresponding odds ratios for deliveries at term were 1.76 (95% confidence interval 1.50-2.06) and 1.18 (95% confidence interval 0.99-1.41). CONCLUSIONS: Both small and large placentas relative to birthweight were associated with fetal death in preterm births. At term, only small placentas relative to birthweight were associated with fetal death. Understanding the mechanisms behind the increased risk of adverse pregnancy outcomes in pregnancies with disproportionate placental weight/birthweight ratio may be important for prevention of fetal deaths.

Placental weight relative to birthweight in pregnancies with maternal diabetes mellitus.

OBJECTIVES: To study the association of maternal diabetes mellitus with placental weight, birthweight and placental weight-to-birthweight ratio. DESIGN: Population-based study. SETTING: Medical Birth Registry of Norway. POPULATION: All singleton births in Norway during 1999-2008 (n = 536,997). METHODS: We compared the distribution of placental weight z-scores and placental weight-to-birthweight ratio between pregnancies with and without diabetes. The associations of diabetes with placental weight z-scores were also estimated as odds ratios with and without adjustment for birthweight, maternal age, parity, preeclampsia, smoking and cesarean delivery. MAIN OUTCOME MEASURES: Placental weight, birthweight and placental weight-to-birthweight ratio. RESULTS: Mean placental weight was 736.6 g in diabetic pregnancies and 672.1 g in non-diabetic pregnancies. The corresponding birthweights were 3682.1 g and 3557.0 g. In diabetic pregnancies, 26.2% of the placentas were in the highest decile of placental weight z-score, as compared with 9.7% in non-diabetic pregnancies (p < 0.001). The corresponding figures for being in the highest decile of placental weight-to-birthweight ratio were 18.2 and 9.9% (p < 0.001). The crude odds ratio for having a placenta in the highest decile of placental weight z-score was 3.29 (95% confidence interval 3.14-3.45) in diabetic pregnancies with non-diabetic pregnancies as the reference. After adjustment for birthweight and other variables, the odds ratio was 2.42 (95% confidence interval 2.29-2.56). CONCLUSIONS: In diabetic pregnancies, placental weight as well as placental weight relative to birthweight were higher than in non-diabetic pregnancies.

Inter-pregnancy interval and placental weight. A population based follow-up study in Norway.

INTRODUCTION: We studied changes in placental weight from the first to the second delivery according to length of the inter-pregnancy interval. METHODS: We followed all women in Norway from their first to their second successive singleton pregnancy during the years 1999-2019, a total of 271 184 women. We used data from the Medical Birth Registry of Norway and studied changes in placental weight (in grams (g)) according to the length of the inter-pregnancy. Adjustments were made for year and maternal age at first delivery, changes in the prevalence of maternal diseases (hypertension and diabetes), and a new father to the second pregnancy. RESULTS: Mean placental weight increased from 655 g at the first delivery to 680 g at the second. The adjusted increase in placental weight was highest at inter-pregnancy intervals <6 months; 38.2 g (95 % CI 33.0g-43.4 g) versus 23.2 g (95 % CI 18.8g-27.7 g) at inter-pregnancy interval 6-17 months. At inter-pregnancy intervals ≥18 months, placental weight remained higher than at the first delivery, but was non-different from inter-pregnancy intervals 6-17 months. Also, after additional adjustment for daily smoking and body mass index in sub-samples, we found the highest increase in placental weight at the shortest inter-pregnancy interval. We estimated no difference in gestational age at delivery or placental to birthweight ratio according to inter-pregnancy interval. DISCUSSION: Placental weight increased from the first to the second pregnancy, and the increase was most pronounced at short inter-pregnancy intervals. The biological causes and implications of such findings remain to be studied.

The impact of maternal age on fetal death: does length of gestation matter?

OBJECTIVE: The objective of the investigation was to study the association of fetal death with maternal age by length of gestation. STUDY DESIGN: This was a population study including all ongoing pregnancies after 16 weeks of gestation in Norway during the period 1967-2006 (n = 2,182,756). RESULTS: The risk of fetal death was 1.4 times higher in women 40-44 years old than in women aged 20-24 years in midpregnancy but 2.8 times higher at term. In term pregnancies the relative importance of maternal age increased by additional pregnancy weeks. In gestational weeks 42-43, the crude risk was 5.1 times higher in mothers 40 years old or older. In the recent period, the elevated risk of fetal death in elderly mothers at term has been attenuated. CONCLUSION: Women 40 years old or older had the highest risk of fetal death throughout pregnancy, particularly in term and postterm pregnancies. Improved obstetric care may explain the attenuation of risk associated with age in recent time.

Validation and development of models using clinical, biochemical and ultrasound markers for predicting pre-eclampsia: an 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 is needed to plan management. OBJECTIVES: To assess the performance of existing pre-eclampsia prediction models and to develop and validate models for pre-eclampsia using individual participant data meta-analysis. We also estimated the prognostic value of individual markers. DESIGN: This was an individual participant data meta-analysis of cohort studies. SETTING: Source data from secondary and tertiary care. PREDICTORS: We identified predictors from systematic reviews, and prioritised for importance in an international survey. PRIMARY OUTCOMES: Early-onset (delivery at < 34 weeks' gestation), late-onset (delivery at ≥ 34 weeks' gestation) and any-onset pre-eclampsia. ANALYSIS: We externally validated existing prediction models in UK cohorts and reported their performance in terms of discrimination and calibration. We developed and validated 12 new models based on clinical characteristics, clinical characteristics and biochemical markers, and clinical characteristics and ultrasound markers in the first and second trimesters. We summarised the data set-specific performance of each model using a random-effects meta-analysis. Discrimination was considered promising for C-statistics of ≥ 0.7, and calibration was considered good if the slope was near 1 and calibration-in-the-large was near 0. Heterogeneity was quantified using I2 and τ2. A decision curve analysis was undertaken to determine the clinical utility (net benefit) of the models. We reported the unadjusted prognostic value of individual predictors for pre-eclampsia as odds ratios with 95% confidence and prediction intervals. RESULTS: The International Prediction of Pregnancy Complications network comprised 78 studies (3,570,993 singleton pregnancies) identified from systematic reviews of tests to predict pre-eclampsia. Twenty-four of the 131 published prediction models could be validated in 11 UK cohorts. Summary C-statistics were between 0.6 and 0.7 for most models, and calibration was generally poor owing to large between-study heterogeneity, suggesting model overfitting. The clinical utility of the models varied between showing net harm to showing minimal or no net benefit. The average discrimination for IPPIC models ranged between 0.68 and 0.83. This was highest for the second-trimester clinical characteristics and biochemical markers model to predict early-onset pre-eclampsia, and lowest for the first-trimester clinical characteristics models to predict any pre-eclampsia. Calibration performance was heterogeneous across studies. Net benefit was observed for International Prediction of Pregnancy Complications first and second-trimester clinical characteristics and clinical characteristics and biochemical markers models predicting any pre-eclampsia, when validated in singleton nulliparous women managed in the UK NHS. History of hypertension, parity, smoking, mode of conception, placental growth factor and uterine artery pulsatility index had the strongest unadjusted associations with pre-eclampsia. LIMITATIONS: Variations in study population characteristics, type of predictors reported, too few events in some validation cohorts and the type of measurements contributed to heterogeneity in performance of the International Prediction of Pregnancy Complications models. Some published models were not validated because model predictors were unavailable in the individual participant data. CONCLUSION: For models that could be validated, predictive performance was generally poor across data sets. Although the International Prediction of Pregnancy Complications models show good predictive performance on average, and in the singleton nulliparous population, heterogeneity in calibration performance is likely across settings. FUTURE WORK: Recalibration of model parameters within populations may improve calibration performance. Additional strong predictors need to be identified to improve model performance and consistency. Validation, including examination of calibration heterogeneity, is required for the models we could not validate. STUDY REGISTRATION: This study is registered as PROSPERO CRD42015029349. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 72. See the NIHR Journals Library website for further project information.

WHAT IS THE PROBLEM?: Pre-eclampsia, a condition in pregnancy that results in raised blood pressure and protein in the urine, is a major cause of complications for the mother and baby. WHAT IS NEEDED?: A way of accurately identifying women at high risk of pre-eclampsia to allow clinicians to start preventative interventions such as administering aspirin or frequently monitoring women during pregnancy. WHERE ARE THE RESEARCH GAPS?: Although over 100 tools (models) have been reported worldwide to predict pre-eclampsia, to date their performance in women managed in the UK NHS is unknown. WHAT DID WE PLAN TO DO?: We planned to comprehensively identify all published models that predict the risk of pre-eclampsia occurring at any time during pregnancy and to assess if this prediction is accurate in the UK population. If the existing models did not perform satisfactorily, we aimed to develop new prediction models. WHAT DID WE FIND?: We formed the International Prediction of Pregnancy Complications network, which provided data from a large number of studies (78 studies, 25 countries, 125 researchers, 3,570,993 singleton pregnancies). We were able to assess the performance of 24 out of the 131 models published to predict pre-eclampsia in 11 UK data sets. The models did not accurately predict the risk of pre-eclampsia across all UK data sets, and their performance varied within individual data sets. We developed new prediction models that showed promising performance on average across all data sets, but their ability to correctly identify women who develop pre-eclampsia varied between populations. The models were more clinically useful when used in the care of first-time mothers pregnant with one child, compared to a strategy of treating them all as if they were at high-risk of pre-eclampsia. WHAT DOES THIS MEAN?: Before using the International Prediction of Pregnancy Complications models in various populations, they need to be adjusted for characteristics of the particular population and the setting of application.

Temporal changes in fetal death risk in pregnancies with preeclampsia: Does offspring birthweight matter? A population study.

OBJECTIVES: To study the associations of preeclampsia with fetal death risk within percentiles of offspring birthweight, and whether these associations have changed during 1967-2014. STUDY DESIGN: In this population study, we included all singleton pregnancies in the Medical Birth Registry of Norway during 1967-2014 (n = 2 607 199). Odds ratios (ORs) for fetal death associated with preeclampsia were estimated within percentiles of birthweight by applying logistic regression analyses. We estimated ORs for the study period as a whole, and for the years 1967-1983 and 1984-2014. RESULTS: During the study period as a whole, preeclampsia increased the risk of fetal death, OR 2.73 (95% CI 2.57-2.89), and the fetal death risk associated with preeclampsia differed across percentiles of offspring birthweight. The overall risk of fetal death decreased during our study period, and the decrease was most prominent in preeclamptic pregnancies with low offspring birthweight (<1 percentile). Thus, in recent years, the risk of fetal death in pregnancies with low offspring birthweight was lower in preeclamptic than in non-preeclamptic pregnancies, OR 0.22 (95% CI 0.12-0.41). Only in pregnancies with offspring birthweight within the 10-90 percentiles, the risk of fetal death associated with preeclampsia remained significantly increased throughout the study period. CONCLUSIONS: The decline in fetal death risk was most prominent in preeclamptic pregnancies with low offspring birthweight. The introduction of a national screening program for preeclampsia in the 1980s, and identification of growth restricted offspring by fetal ultrasonography, may explain our findings.

Placental weight and birthweight: the relations with number of daily cigarettes and smoking cessation in pregnancy. A population study.

Background: We studied associations of number of daily cigarettes in the first trimester with placental weight and birthweight in women who smoked throughout pregnancy, and in women who stopped smoking after the first trimester. Methods: We included all women with delivery of a singleton in Norway (n = 698 891) during 1999-2014, by using data from the Medical Birth Registry of Norway. We assessed dose-response associations by applying linear regression with restricted cubic splines. Results: In total, 12.6% smoked daily in the first trimester, and 3.7% stopped daily smoking. In women who smoked throughout pregnancy, placental weight and birthweight decreased by number of cigarettes; however, above 11-12 cigarettes we estimated no further decrease (Pnon-linearity < 0.001). Maximum decrease in placental weight in smokers compared with non-smokers was 18.2 g [95% confidence interval (CI): 16.6 to 19.7], and for birthweight the maximum decrease was 261.9 g (95% CI: 256.1 to 267.7). In women who stopped smoking, placental weight was higher than in non-smokers and increased by number of cigarettes to a maximum of 16.2 g (95% CI: 9.9 to 22.6). Birthweight was similar in women who stopped smoking and non-smokers, and we found no change by number of cigarettes (Pnon-linearity < 0.001). Conclusions: In women who smoked throughout pregnancy, placental weight and birthweight decreased non-linearly by number of cigarettes in the first trimester. In women who stopped smoking, placental weight was higher than in non-smokers and increased linearly by number of cigarettes; birthweight was almost similar to that of non-smokers.

Placental weight in the first pregnancy and risk for preeclampsia in the second pregnancy: A population-based study of 186 859 women.

OBJECTIVE: To study whether placental weight in the first pregnancy is associated with preeclampsia in the second pregnancy. STUDY DESIGN: In this population-based study, we included all women with two consecutive singleton pregnancies reported to the Medical Birth Registry of Norway during 1999-2012 (n=186 859). Placental weight in the first pregnancy was calculated as z-scores, and the distribution was divided into five groups of equal size (quintiles). We estimated crude and adjusted odds ratios with 95% confidence intervals for preeclampsia in the second pregnancy according to quintiles of placental weight z-scores in the first pregnancy. The 3rd quintile was used as the reference group. RESULTS: Among women without preeclampsia in the first pregnancy, 1.4% (2507/177 149) developed preeclampsia in the second pregnancy. In these women, the risk for preeclampsia in the second pregnancy was associated with placental weight in the first pregnancy in both lowest (crude odds ratio (cOR) 1.30, 95% confidence interval (CI); 1.14-1.47) and highest quintile (cOR 1.20, 95% CI; 1.06-1.36). The risk associated with the highest quintile of placental weight was confined to term preeclampsia. Among women with preeclampsia in the first pregnancy, 15.7% (1522/9710) developed recurrent preeclampsia, and the risk for recurrent preeclampsia was associated with placental weight in lowest quintile in the first pregnancy (cOR 1.30, 95% CI; 1.10-1.55). Adjustment for interval between pregnancies, maternal diabetes, age, and smoking in the first pregnancy did not alter these estimates notably. CONCLUSION: Placental weight in the first pregnancy might help to identify women who could be at risk for developing preeclampsia in a second pregnancy.