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Objectives To investigate the risk of stillbirth in relation to; 1) a previous CD compared to those following a vaginal birth (VB); and 2) vaginal birth after caesarean (VBAC) compared to a repeat CD. Design Population-based cohort study. Setting The Swedish Medical Birth registry Population Women with their first and second singletons between 1982 and 2012. Methods Multivariable logistic regression models were performed to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) of the association between CD in the first pregnancy and stillbirth in the second pregnancy and the association between VBAC and stillbirth. Sub-group analyses were performed by types of CD and timing of stillbirth (antepartum and intrapartum). Main outcome measures Stillbirth (antepartum and intrapartum fetal death). Results Of the 1,771,700 singleton births from 885,850 women,117,114 (13.2%) women had a CD in the first pregnancy, and 51,755 had VBAC in the second pregnancy. We found a 37% increased odds of stillbirth (aOR:1.37 [95% CI, 1.23–1.52]) in women with a previous CD compared to VB. The odds of intrapartum stillbirth was higher in previous pre-labour CD group (aOR:2.72 [95% CI, 1.51–4.91]) than the previous in-labour CD group (aOR:1.35 [95% CI, 0.76–2.40,]), although not statistically significant in the latter case. No increased odds was found for intrapartum stillbirth in women who had VBAC (aOR:0.99 [95% CI, 0.48–2.06]) compared to women who had a repeat CD, whereas women with antepartum stillbirth were more likely to have a VBAC (aOR:4.49 [95% CI, 3.55–5.67]). Conclusions This study confirms that a CD is associated with an increased risk of subsequent stillbirth, with a greater risk among pre-labour CD. This association is not solely mediated by increases in intrapartum asphyxia, uterine rupture or attempted VBAC. Further research is needed to understand this association, but these findings might help health care providers to reach optimal decisions regarding mode of birth, particularly when CD is unnecessary.

Background and Aims Gestational diabetes (GDM) is increasingly common worldwide. GDM is associated with increased risk of type 2 diabetes (T2DM) and cardiovascular disease in women. It is uncertain whether GDM is independently associated with long-term risk of maternal kidney disease. We aimed to examine the association between GDM and maternal chronic kidney disease (CKD) and end-stage kidney disease (ESKD) and to determine whether this depends on progression to overt T2DM. Method A nationwide retrospective cohort study was designed using data from the Swedish national registers. Women were included if their first delivery occurred between 1 January 1987 and 31 December 2012. Previous GDM was the main exposure variable, and this was stratified according to whether women developed T2DM after pregnancy. We estimated the risk of CKD, ESKD and different CKD subtypes (tubulointerstitial, glomerular, hypertensive, diabetic, other/non-specific). Cox-proportional hazard regression models were used with time-dependent covariates. We adjusted for a wide range of confounders including maternal age, country of origin, maternal education, parity, antenatal BMI, gestational weight gain, smoking during pregnancy and preeclampsia. Results There were 1,121,633 women included, of whom 15,595 (1.4%) had a diagnosis of GDM. Overall, GDM-diagnosed women were at increased risk of CKD (aHR 1.81, 95% CI 1.54-2.14) and ESKD (aHR 4.52, 95% CI 2.75-7.44). Associations were strongest for diabetic CKD (aHR 8.81, 95% CI 6.36-12.19), hypertensive CKD (aHR 2.46, 95% CI 1.06-5.69), and glomerular CKD (aHR 1.86, 95% CI 1.37-2.51). However, these associations were largely explained by progression to post-pregnancy T2DM. Among women who had GDM + subsequent T2DM, strong associations were observed with CKD (aHR 21.70, 95% CI 17.17-27.42) and ESKD (aHR 112.37, 95% CI 61.22-206.38). By contrast, women who only experienced GDM (and no future T2DM) were not at significantly higher risk of CKD (aHR 1.11, 95% CI 0.89-1.38) or ESKD (aHR 1.58, 95% CI 0.70-3.60). Conclusion Women who experience GDM are at increased risk of CKD and ESKD if they develop T2DM. However, GDM-diagnosed women who do not develop overt T2DM in later life have a similar risk of CKD/ESKD to those with uncomplicated pregnancies.

Background Maternal chronic kidney disease and chronic hypertension have been linked with adverse pregnancy outcomes. We aimed to examine the association between these conditions and adverse pregnancy outcomes over the last 3 decades. Objective We conducted this national cohort study to assess the association between maternal chronic disease (CH, CKD or both conditions) and adverse pregnancy outcomes with an emphasis on the effect of parity, maternal age, and BMI on these associations over the last three decades. We further investigated whether different subtypes of CKD had differing effects. Study Design We used data from the Swedish Medical Birth Register, including 2,788,490 singleton births between 1982 and 2012. Women with chronic kidney disease and chronic hypertension were identified from the Medical Birth Register and National Patient Register. Logistic regression models were performed to assess the associations between maternal chronic disease (chronic hypertension, chronic kidney disease, or both conditions) and pregnancy outcomes, including preeclampsia, in-labor and prelabor cesarean delivery, preterm birth, small for gestational age, and stillbirth. Results During the 30-year study period, 22,397 babies (0.8%) were born to women with chronic kidney disease, 13,279 (0.48%) to women with chronic hypertension and 1079 (0.04%) to women with both conditions. Associations with chronic hypertension were strongest for preeclampsia (adjusted odds ratio, 4.57; 95% confidence interval, 4.33–4.84) and stillbirth (adjusted odds ratio, 1.65; 95% confidence interval, 1.35–2.03) and weakest for spontaneous preterm birth (adjusted odds ratio, 1.07; 95% confidence interval, 0.96–1.20). The effect of chronic kidney disease varied from (adjusted odds ratio, 2.05; 95% confidence interval, 1.92–2.19) for indicated preterm birth to no effect for stillbirth (adjusted odds ratio, 1.16; 95% confidence interval, 0.95–1.43). Women with both conditions had the strongest associations for in-labor cesarean delivery (adjusted odds ratio, 1.86; 95% confidence interval, 1.49–2.32), prelabor cesarean delivery (adjusted odds ratio, 2.68; 95% confidence interval, 2.18–3.28), indicated preterm birth (adjusted odds ratio, 9.09; 95% confidence interval, 7.61–10.7), and small for gestational age (adjusted odds ratio, 4.52; 95% confidence interval, 3.68–5.57). The results remained constant over the last 3 decades. Stratified analyses of the associations by parity, maternal age, and body mass index showed that adverse outcomes remained independently higher in women with these conditions, with worse outcomes in multiparous women. All chronic kidney disease subtypes were associated with higher odds of preeclampsia, in-labor cesarean delivery, and medically indicated preterm birth. Different subtypes of chronic kidney disease had differing risks; strongest associations of preeclampsia (adjusted odds ratio, 3.98; 95% confidence interval, 2.98–5.31) and stillbirth (adjusted odds ratio, 2.73; 95% confidence interval, 1.13–6.59) were observed in women with congenital kidney disease, whereas women with diabetic nephropathy had the most pronounced increase odds of in-labor cesarean delivery (adjusted odds ratio, 3.54; 95% confidence interval, 2.06–6.09), prelabor cesarean delivery (adjusted odds ratio, 7.50; 95% confidence interval, 4.74–11.9), and small for gestational age (adjusted odds ratio, 4.50; 95% confidence interval, 2.92–6.94). In addition, women with renovascular disease had the highest increased risk of preterm birth in both spontaneous preterm birth (adjusted odds ratio, 3.01; 95% confidence interval, 1.57–5.76) and indicated preterm birth (adjusted odds ratio, 8.09; 95% confidence interval, 5.73–11.4). Conclusion Women with chronic hypertension, chronic kidney disease, or both conditions are at an increased risk of adverse pregnancy outcomes which were independent of maternal age, body mass index, and parity. Multidisciplinary management should be provided with intensive clinical follow-up to support these women during pregnancy, particularly multiparous women. Further research is needed to evaluate the effect of disease severity on adverse pregnancy outcomes.

Background Preeclampsia is associated with increased risk of future cardiovascular disease, but evidence for associations with chronic kidney disease (CKD) has been inconsistent to date. We aimed to measure associations between preeclampsia and long-term CKD in a population-based sample of parous women, and to identify whether the risk differs by CKD subtype. Methods Using data from the Swedish Medical Birth Register, singleton live births from 1973-2012 were identified and linked to data from the Swedish Renal Register and National Patient Register (up to 2013). Preeclampsia was the main exposure of interest and was treated as a time-dependent variable. The primary outcome was maternal CKD, and this was classified into 5 subtypes: hypertensive, diabetic, glomerular/proteinuric, tubulo-interstitial, other/non-specific CKD. Cox proportional hazard regression models were used for analysis. Women with pre-pregnancy comorbidities were excluded. Results The dataset included 1,924,591 unique women who had 3,726,819 singleton pregnancies. The median follow-up was 20.7 (interquartile range 9.9-30.0) years. Overall, 90,964 women (4.7%) experienced preeclampsia and 18,146 (0.9%) developed CKD. Women who had preeclampsia had higher risk of developing any CKD during follow-up (aHR 1.88, 95% CI 1.79-1.98). The risk differed by CKD subtype, and was higher for hypertensive CKD (aHR 3.76, aHR 3.09-4.57), diabetic CKD (aHR 3.45, 95% CI 2.83-4.21) and glomerular/proteinuric CKD (aHR 2.08, 95% CI 1.90-2.29). Women who had preterm preeclampsia, recurrent preeclampsia, or preeclampsia complicated by pre-pregnancy obesity were also at greater risk of any CKD. Conclusions Women with a history of preeclampsia are at increased risk of long-term CKD. The risk is most marked for hypertensive CKD, diabetic CKD, and glomerular/proteinuric CKD. The absolute risk of CKD related to preeclampsia is substantial, and these women may warrant systematic renal monitoring in the years following delivery. Key messages Preeclampsia is an independent predictor of long-term risk of chronic kidney disease in otherwise healthy parous women. Women with a history of preeclampsia may warrant systematic renal monitoring through additional blood pressure, blood glucose, and proteinuria checks.

Background Chronic hypertension (CH) has been linked with adverse pregnancy outcomes, but it is unclear whether these associations are changing by maternal characteristics or over time. The objective of this study was to examine the association between maternal CH and adverse pregnancy outcomes, and to determine whether the risk varies over time. We also aimed to assess the associations according to maternal age (younger or ≥ 35 yrs.) and other maternal characteristics. Methods This population-based cohort study included women who had singleton births in Sweden between 1982 and 2012. Using data from the Medical Birth Register, we identified 2,777,045 babies born to 1,417,903 mothers during the study period. Of those 9,334 were born to women with CH. Maternal CH were recorded using ICD-8, ICD-9 and ICD-10. Outcome measures were pre-eclampsia (PE), emergency and elective caesarean sections (CS), spontaneous preterm birth (PTB Results Compared to normotensive women, we found higher odds among hypertensive women of the following outcomes: PE adjusted odds ratio [aOR (95% confidence intervals)]: [4.60 (4.31, 4.92)]; emergency CS [1.64 (1.53, 1.77)]; elective CS [1.63 (1.51, 1.76)]; medically indicated PTB [3.36 (3.11, 3.63)]; stillbirth [1.62 (1.26, 2.08)] and SGA [2.33 (2.13, 2.54)]. Moreover, Women of advanced maternal age were more likely to have emergency CS [aOR: 1.82 (1.61, 2.05)]; elective CS [1.83 (1.64, 2.04)]; medically indicated PTB [4.01 (3.54, 4.54)] and SGA [2.61 (2.24, 3.04)] compared to younger normotensive women. However, the magnitude of these associations appears to decrease over time apart of the association with PE which appears to have remained almost constant over time. Conclusion Women with chronic hypertension are at increased risk of adverse maternal, fetal and neonatal outcomes and the risk differs according to maternal age. However, the effect of antihypertensive treatment and severity of hypertension have not been taken into account in this study.

Background Hypertensive disorders of pregnancy (HDP) (preeclampsia, gestational hypertension) are increasingly common complications of pregnancy. HDP are associated with increased risk of cardiovascular disease and end-stage kidney disease in women. Chronic kidney disease (CKD) is highly prevalent, but evidence for associations between HDP and CKD is limited and inconsistent. The underlying causes of CKD are wide-ranging, and HDP may have differential associations with various aetiologies of CKD. We aimed to identify whether HDP are associated with CKD and whether this risk differs by CKD aetiology. Methods Using data from the Swedish Medical Birth Register, singleton live births from 1973–2012 were identified and linked to data from the Swedish Renal Register and National Patient Register (up to 2013). Preeclampsia was the main exposure of interest and treated as a time-dependent variable. Gestational hypertension was also investigated as a secondary exposure. The primary outcome was maternal CKD, and this was classified into 5 subtypes: hypertensive, diabetic, glomerular/proteinuric, tubulo-interstitial, other/non-specific CKD. Cox proportional hazard regression models were used, adjusting for year of delivery, maternal age, country of origin, education level, antenatal BMI, smoking during pregnancy, gestational diabetes, and parity. Women with pre-pregnancy comorbidities were excluded. Results The final sample consisted of 1,924,409 women who had 3,726,554 singleton live-births. The mean age of women at first delivery was 27.0 (±5.1) years. Median follow-up was 20.7 (interquartile range 9.9–30.0) years. 90,917 women (4.7%) were diagnosed with preeclampsia, 43,964 (2.3%) had gestational hypertension, and 18,477 (0.9%) developed CKD. Women who had preeclampsia had a higher risk of developing CKD during follow-up (adjusted hazard ratio (aHR) 1.92, 95% CI 1.83–2.03). The risk differed by CKD subtype, and was higher for hypertensive CKD (aHR 3.72, 95% CI 3.05–4.53), diabetic CKD (aHR 3.94, 95% CI 3.38–4.60) and glomerular/proteinuric CKD (aHR 2.06, 95% CI 1.88–2.26). The risk of CKD was increased after preterm preeclampsia, recurrent preeclampsia, or preeclampsia complicated by pre-pregnancy obesity. Women who had gestational hypertension also had increased risk of developing CKD (aHR 1.49, 95% CI 1.38–1.61). Conclusion Women with history of HDP are at increased risk of CKD, particularly hypertensive or diabetic CKD. Preterm preeclampsia, recurrent preeclampsia, and preeclampsia complicated by pre-pregnancy obesity are all associated with higher risk of maternal CKD. Since 10% of women develop clinically significant CKD in their lifetime, the absolute risk of CKD related to HDP may be substantial. Women who experience HDP may benefit from future systematic renal monitoring to prevent CKD onset or progression.

Background Little is known about the long-term risk of renal disease following adverse pregnancy outcomes, such as hypertensive disorders of pregnancy (HDP), gestational diabetes (GDM) or preterm delivery. We aimed to investigate associations between adverse pregnancy outcomes and maternal chronic kidney disease (CKD) and end-stage kidney disease (ESKD), by synthesising results of relevant studies. Methods A systematic search of PubMed, EMBASE and Web of Science was done up to July 2018. Case-control and cohort studies were eligible for inclusion if they provided original effect estimates for associations between adverse pregnancy outcomes (HDP, GDM, preterm) and maternal renal disease (primary outcomes: CKD, ESKD; secondary outcomes: renal hospitalisation, renal mortality). Two independent reviewers extracted data and assessed risk of bias. Random effects meta-analyses were conducted to determine pooled adjusted odds ratio (AOR) and 95% confidence interval (95%CI) for each association. Results Of 5,120 studies retrieved, 21 studies met inclusion criteria (4,483,847 participants). HDP was associated with increased odds of ESKD (AOR 6.58, 95%CI 4.06-10.65), CKD (AOR 2.08, 95%CI 1.06-4.10), renal hospitalisation (AOR 2.29, 95%CI 1.42-3.71). The magnitude of association was dependent on HDP subtype: AOR for preeclampsia and ESKD was 4.87 (95%CI 3.01-7.87); gestational hypertension and ESKD was 3.65 (95%CI 2.34-5.67); other HDP (including chronic hypertension) and ESKD was 14.67 (95%CI 3.21-66.97). Preterm delivery was associated with increased odds of ESKD (AOR 2.16, 95%CI 1.64-2.85). GDM was associated with increased odds of CKD among black women (AOR 1.78, 95%CI 1.18-2.70), but not Caucasian women (AOR 0.81, 95%CI 0.58-1.13) Conclusions Women who experience adverse pregnancy outcomes have increased odds of renal disease, especially after HDP. Risk stratification and preventive interventions may be needed to reduce the risk of clinically significant renal disease in mothers. Key messages This is the first study to summarise the long-term risk of renal disease among women who experience a range of adverse pregnancy outcomes. Women who experience hypertensive disorders in pregnancy, preterm delivery, or gestational diabetes are at increased odds of renal disease.

Background Preterm delivery is an independent risk factor for maternal cardiovascular disease. Little is known about the association between preterm delivery and maternal renal function, and whether any association is independent of preeclampsia or intra-uterine growth restriction. This study aimed to examine the association between gestational age and long-term maternal chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Methods Using data from the Swedish Medical Birth Register, singleton live births from 1973-2012 were identified and linked to data from the Swedish Renal Register and National Patient Register (up to 2013). Women with pre-pregnancy CKD/ESKD, cardiovascular disease, diabetes, hypertension, systemic lupus erythematosus were excluded. Gestational age at delivery was the main exposure, treated as a time-dependent variable. Primary outcomes were maternal CKD or ESKD. Cox regression was used, adjusting for maternal age, year of delivery, country of origin, education, parity, interpregnancy interval, smoking, BMI, gestational diabetes. Models were stratified by exposure to preeclampsia or small for gestational age (SGA). Results There were 3,847,694 pregnancies among 1,990,273 unique women. Nine percent of women (n = 172,915) had at least one preterm delivery ( Conclusions Women who gave birth at earlier gestation were at higher risk of later CKD and ESKD. This association persisted independently of preeclampsia and SGA. Key messages Preterm delivery is an independent predictor of long-term maternal renal disease. Obstetric history should be considered as part of overall risk stratification for chronic kidney disease in women.

Background Adverse pregnancy outcomes, like hypertensive disorders of pregnancy (HDP), gestational diabetes (GDM) and preterm delivery, are associated with increased risk of long-term maternal cardiovascular and cerebrovascular disease. Comparatively little is known about whether adverse pregnancy outcomes increase the risk of maternal renal disease. We aimed to investigate associations between adverse pregnancy outcomes (HDP, GDM, preterm delivery) and long-term maternal chronic kidney disease (CKD) and end-stage kidney disease (ESKD), by synthesising the results of relevant published studies. Methods A systematic search of PubMed, EMBASE and Web of Science was undertaken from inception of databases to 31 July 2018. Case-control and cohort studies published in English were eligible for inclusion if they provided original effect estimates for associations between adverse pregnancy outcomes (HDP, GDM, preterm delivery) and maternal renal disease (primary outcomes: CKD, ESKD; secondary outcomes: renal hospitalisation, mortality due to renal disease). Two independent reviewers extracted data and assessed risk of bias. Random effects meta-analyses were conducted using RevMan 5.3 to determine the pooled adjusted odds ratio (AOR) and 95% confidence interval (95%CI) for each association between each adverse pregnancy outcome and CKD or ESKD respectively. Subgroup analysis by HDP subtype was performed. Results Of 5,120 studies retrieved, 21 studies met inclusion criteria (37 adjusted effect estimates in total, including 4,483,847 participants). HDP was associated with significantly increased odds of ESKD (AOR 6.58, 95%CI 4.06–10.65, based on nine effect estimates), CKD (AOR 2.08, 95%CI 1.06–4.10, based on eight estimates), and renal hospitalisation (AOR 2.29, 95%CI 1.42–3.71, based on six estimates). The magnitude of association was dependent on HDP subtype: AOR for preeclampsia and ESKD was 4.87 (95%CI 3.01–7.87); for gestational hypertension and ESKD was 3.65 (95%CI 2.34–5.67); for other HDP (including chronic hypertension ± superimposed preeclampsia) and ESKD was 14.67 (95%CI 3.21–66.97). Preterm delivery was associated with increased odds of ESKD (AOR 2.16, 95%CI 1.64–2.85, based on three estimates). GDM was associated with increased odds of CKD among black women (AOR 1.78, 95%CI 1.18–2.70), but not white/Caucasian women (AOR 0.81, 95%CI 0.58–1.13, based on four estimates). Conclusion Women who experience adverse pregnancy outcomes have increased odds of long-term renal disease, particularly those exposed to HDP. This study was limited by small numbers of studies in each individual meta-analysis, restricting the ability to assess for publication bias. Long-term follow-up should be optimised for women who experience adverse pregnancy outcomes, and preventive interventions may be warranted to reduce their risk of clinically significant renal disease.

Background Preeclampsia has been suggested to increase the risk of end-stage kidney disease (ESKD); however, most studies were unable to adjust for potential confounders including pre-existing comorbidities such as renal disease and cardiovascular disease (CVD). We aimed to examine the association between preeclampsia and the risk of ESKD in healthy women, while taking into account pre-existing comorbidity and potential confounders. Methods and findings Using data from the Swedish Medical Birth Register (MBR), women who had singleton live births in Sweden between 1982 and 2012, including those who had preeclampsia, were identified. Women with a diagnosis of chronic kidney disease (CKD), CVD, hypertension, or diabetes prior to the first pregnancy were excluded. The outcome was a diagnosis of ESKD, identified from the Swedish Renal Registry (SRR) from January 1, 1991, onwards along with the specified cause of renal disease. We conducted Cox proportional hazards regression analysis to examine the association between preeclampsia and ESKD adjusting for several potential confounders: maternal age, body mass index (BMI), education, native country, and smoking. This analysis accounts for differential follow-up among women because women had different lengths of follow-up time. We performed subgroup analyses according to preterm preeclampsia, small for gestational age (SGA), and women who had 2 pregnancies with preeclampsia in both. The cohort consisted of 1,366,441 healthy women who had 2,665,320 singleton live births in Sweden between 1982 and 2012. At the first pregnancy, women’s mean (SD) age and BMI were 27.8 (5.13) and 23.4 (4.03), respectively, 15.2% were smokers, and 80.7% were native Swedish. The overall median (interquartile range [IQR]) follow-up was 7.4 years (3.2–17.4) and 16.4 years (10.3–22.0) among women with ESKD diagnosis. During the study period, 67,273 (4.9%) women having 74,648 (2.8% of all pregnancies) singleton live births had preeclampsia, and 410 women developed ESKD with an incidence rate of 1.85 per 100,000 person-years. There was an association between preeclampsia and ESKD in the unadjusted analysis (hazard ratio [HR] = 4.99, 95% confidence interval [CI] 3.93–6.33; p < 0.001), which remained in the extensively adjusted (HR = 4.96, 95% CI 3.89–6.32, p < 0.001) models. Women who had preterm preeclampsia (adjusted HR = 9.19; 95% CI 5.16–15.61, p < 0.001) and women who had preeclampsia in 2 pregnancies (adjusted HR = 7.13, 95% CI 3.12–16.31, p < 0.001) had the highest risk of ESKD compared with women with no preeclampsia. Considering this was an observational cohort study, and although we accounted for several potential confounders, residual confounding cannot be ruled out. Conclusions The present findings suggest that women with preeclampsia and no major comorbidities before their first pregnancy are at a 5-fold increased risk of ESKD compared with parous women with no preeclampsia; however, the absolute risk of ESKD among women with preeclampsia remains small. Preeclampsia should be considered as an important risk factor for subsequent ESKD. Whether screening and/or preventive strategies will reduce the risk of ESKD in women with adverse pregnancy outcomes is worthy of further investigation., Ali S Khashan and colleagues reveal an increased risk for kidney disease in women who had pre-eclampsia during pregnancy., Author summary Why was this study done? A large number of studies reported an increased risk of cardiovascular disease (CVD) among women who had preeclampsia compared with women who had no preeclampsia. Only few studies reported such as association between preeclampsia and the risk of developing end-stage kidney disease (ESKD). Some of these studies did not adjust for key potential confounders and may have lacked high-quality data. What did the researchers do and find? We performed this study to examine the association between preeclampsia and ESKD using a large cohort from the Swedish national registers (N = 1,366,441 healthy women who had 2,665,320 singleton live births). We found that women who had preeclampsia in at least one pregnancy, were 5 times more likely to have ESKD compared with parous women who had never had preeclampsia (hazard ratio [HR] = 4.96, 95% confidence interval [CI] 3.89–6.32). This association was independent of several sociodemographic factors such as maternal age and education and prepregnancy comorbidity such as renal disease and CVD. What do these findings mean? These results highlight the importance of preeclampsia as a risk marker for developing ESKD. These findings need to be investigated further to see whether preventive strategies would reduce the risk of ESKD.

Amniotic fluid (AF) surrounds the growing fetus, and cells derived from AF are commonly used for diagnosis of genetic diseases. Intra-amniotic infections are strongly linked to preterm birth, which is the leading cause of perinatal mortality worldwide. Surprisingly little is known, however, about mature hematopoietic cells in AF, which could potentially be involved in immune responses during pregnancy. In this study, we show that the dominating population of viable CD45+ cells in AF is represented by a subset of fetal CD103+ group 3 innate lymphoid cells (ILCs) producing high levels of IL-17 and TNF. Fetal CD103+ ILC3s could also be detected at high frequency in second-trimester mucosal tissues (e.g., the intestine and lung). Taken together, our data indicate that CD103+ ILC3s accumulate with gestation in the fetal intestine and subsequently egress to the AF. The dominance of ILC3s producing IL-17 and TNF in AF suggests that they could be involved in controlling intra-amniotic infections and inflammation and as such could be important players in regulating subsequent premature birth.

Importance Adverse pregnancy outcomes, such as hypertensive disorders of pregnancy, gestational diabetes, and preterm delivery, are associated with increased risk of maternal cardiovascular disease. Little is known about whether adverse pregnancy outcomes are associated with increased risk of maternal chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Objective To review and synthesize the published literature on adverse pregnancy outcomes (hypertensive disorders of pregnancy, gestational diabetes, and preterm delivery) and subsequent maternal CKD and ESKD. Data Sources PubMed, Embase, and Web of Science were searched from inception to July 31, 2019, for cohort and case-control studies of adverse pregnancy outcomes and maternal CKD and ESKD. Study Selection Selected studies included the following: a population of pregnant women, exposure to an adverse pregnancy outcome of interest, and at least 1 primary outcome (CKD or ESKD) or secondary outcome (hospitalization or death due to kidney disease). Adverse pregnancy outcomes included exposure to hypertensive disorders of pregnancy (preeclampsia, gestational hypertension, or chronic hypertension), preterm delivery ( Data Extraction and Synthesis The Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines were followed throughout. Three reviewers extracted data and appraised study quality. Random-effects meta-analyses were used to calculate overall pooled estimates using the generic inverse variance method. Main Outcomes and Measures Primary outcomes included CKD and ESKD diagnosis, defined using established clinical criteria (estimated glomerular filtration rate or albuminuria values) or hospital records. The protocol for this systematic review was registered on PROSPERO (CRD42018110891). Results Of 23 studies included (5 769 891 participants), 5 studies reported effect estimates for more than 1 adverse pregnancy outcome. Preeclampsia was associated with significantly increased risk of CKD (pooled adjusted risk ratio [aRR], 2.11; 95% CI, 1.72-2.59), ESKD (aRR, 4.90; 95% CI, 3.56-6.74), and kidney-related hospitalization (aRR, 2.65; 95% CI, 1.03-6.77). Gestational hypertension was associated with increased risk of CKD (aRR, 1.49; 95% CI, 1.11-2.01) and ESKD (aRR, 3.64; 95% CI, 2.34-5.66). Preterm preeclampsia was associated with increased risk of ESKD (aRR, 5.66; 95% CI, 3.06-10.48); this association with ESKD persisted for women who had preterm deliveries without preeclampsia (aRR, 2.09; 95% CI, 1.64-2.66). Gestational diabetes was associated with increased risk of CKD among black women (aRR, 1.78; 95% CI, 1.18-2.70), but not white women (aRR, 0.81; 95% CI, 0.58-1.13). Conclusions and Relevance In this meta-analysis, exposure to adverse pregnancy outcomes, including hypertensive disorders of pregnancy, gestational diabetes, and preterm delivery, was associated with higher risk of long-term kidney disease. The risk of ESKD was highest among women who experienced preeclampsia. A systematic approach may be warranted to identify women at increased risk of kidney disease, particularly after hypertensive disorders of pregnancy, and to optimize their long-term follow-up.

Objective To estimate the cost-effectiveness of first trimester non-invasive fetal RHD screening for targeted antenatal versus no routine antenatal anti-D prophylaxis (RAADP) or versus non-targeted RAADP. Design Model based on a population-based cohort study. Setting The Swedish health service. Population Intervention subjects in the underlying cohort study were RhD-negative pregnant women receiving first trimester fetal RHD screening followed by targeted anti-D in 2010–2011 (n = 6723). Historical comparators were RhD-negative women who delivered in 2008–2009 when standard care did not include RAADP (n = 7099). Methods Healthcare costs for the three strategies were included for the first and subsequent pregnancies. For the comparison with non-targeted RAADP, the immunisation rate was based on the observed rate for targeted therapy and adjusted downwards by removing the influence of false negatives. Main outcome measure Additional cost per RhD immunisation averted. Results Compared with RAADP, targeted prophylaxis was associated with fewer immunisations (0.19 versus 0.46% per pregnancy) and lower costs (cost-savings of €32 per RhD-negative woman). The savings were from lower costs during pregnancy and delivery, and lower costs of future pregnancies through fewer immunisations. Non-targeted anti-D was estimated to result in 0.06% fewer immunisations and an additional €16 in cost-savings per mother, compared with targeted anti-D. Conclusion Based on effect data from a population-based cohort study, targeted prophylaxis was associated with lower immunisation risk and costs versus no RAADP. Based on effect data from theoretical calculations, non-targeted RAADP was predicted to result in lower costs and immunisation risk compared with targeted prophylaxis. Tweetable abstract Fetal RHD screening and targeted prophylaxis resulted in lower immunisation risk and costs compared with no RAADP.

Objective To evaluate the effect of a newly developed training curriculum on the performance of fetoscopic laser surgery for twin–twin transfusion syndrome (TTTS) using an advanced high-fidelity simulator model. Methods Ten novices were randomized to receive verbal instructions and either skills training using the simulator (study group; n = 5) or no training (control group; n = 5). Both groups were evaluated with a pre-training and post-training test on the simulator. Performance was assessed by two independent observers and comprised a 52-item checklist for surgical performance (SP) score, measurement of procedure time and number of anastomoses missed. Eleven experts set the benchmark level of performance. Face validity and educational value of the simulator were assessed using a questionnaire. Results Both groups showed an improvement in SP score at the post-training test compared with the pre-training test. The simulator-trained group significantly outperformed the control group, with a median SP score of 28 (54%) in the pre-test and 46 (88%) in the post-test vs 25 (48%) and 36 (69%), respectively (P = 0.008). Procedure time decreased by 11 min (from 44 to 33 min) in the study group vs 1 min (from 39 to 38 min) in the control group (P = 0.69). There was no significant difference in the number of missed anastomoses at the post-training test between the two groups (1 vs 0). Subsequent feedback provided by the participants indicated that training on the simulator was perceived as a useful educational activity. Conclusions Proficiency-based simulator training improves performance, indicated by SP score, for fetoscopic laser therapy. Despite the small sample size of this study, practice on a simulator is recommended before trainees carry out laser therapy for TTTS in pregnant women. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Objective To evaluate the performance and cost efficacy of different first-trimester contingent screening strategies based on an initial analysis of biochemical markers. Design Retrospective study. Setting Swedish National Quality Register for prenatal diagnosis. Population 35 780 women with singleton pregnancies. Methods Serum values from first trimester biochemistry were re-analyzed in a contingent approach. For risks between 1:40 and 1:1000, risk estimates from nuchal translucency measurements were added and outcomes were compared using either a final cut-off risk of 1:200 to proceed with invasive testing or offering non-invasive prenatal testing. In a subgroup of 12 836 women with regular menstrual cycles the same analyses were performed using data on the last menstrual period for determining gestational age. The costs of detecting one case of aneuploidy were compared. Main outcome measures Comparison of screening strategies. Results The detection rate was the same (87%) in the contingent group as in complete combined screening, with only 41% requiring a nuchal translucency scan. As an alternative, offering non-invasive prenatal testing to the intermediate risk group would result in a detection rate of 98%, but the cost to detect one case of trisomy 21 would be 83% higher than the cost associated with traditional combined screening. Conclusions First trimester examination using a contingent approach will achieve similar results compared with full combined screening. Non-invasive prenatal testing will not be cost-effective when a high proportion of pregnancies need further testing.

Invasive fetal therapy Invasive fetal therapy in Sweden consists of fetoscopic interventions to treat twin-to-twin transfusion syndrome (TTS) or twin anemia polycytemia sequence (TAPS) in monochorionic twin or triplet pregnancies and for selective reduction in monochorionic twins complicated by discordant anomalies or severe growth retardation in one fetus. Alternative methods, such as intrafetal laser ablation and radio frequency ablation, are also used for selective reduction and rarely to treat fetal tumors. Ultrasound guided intrauterine blood transfusions to treat fetal anemia have been performed for a long time with excellent results. Placement of thoraco-amniotic shunts and vesico-amniotic shunts is indicated in a few cases per year in Sweden. Since these rare interventions were centralized to one national center in 2013, the outcome of the fetal interventions has improved consistently.

Background Stillbirth is a devastating adverse pregnancy outcome that may occur without any obvious reason or may occur in the context of fetal growth restriction, preeclampsia, or other obstetric complications. There is increasing evidence that women who experience stillbirths are at greater risk of long-term cardiovascular disease, but little is known about their risk of chronic kidney disease and end-stage renal disease. We conducted the largest study to date to investigate the subsequent risk of maternal chronic kidney disease and end-stage renal disease following stillbirth. Objective To identify whether pregnancy complicated by stillbirth is associated with subsequent risk of maternal chronic kidney disease and end-stage renal disease, independent of underlying medical or obstetric comorbidities. Study Design/Methods We conducted a population-based cohort study using nationwide data from the Swedish Medical Birth Register, National Patient Register, and Swedish Renal Register. We included all women who had live births and stillbirths from 1973 to 2012, with follow-up to 2013. Women with preexisting renal disease were excluded. Cox proportional hazard regression models were used to estimate adjusted hazard ratios and 95% confidence intervals for associations between stillbirth and maternal chronic kidney disease and end-stage renal disease respectively. We controlled for maternal age, year of delivery, country of origin, parity, body mass index, smoking, gestational diabetes, preeclampsia, and small for gestational age deliveries. Women who had a history of medical comorbidities, which may predispose to renal disease (prepregnancy cardiovascular disease, hypertension, diabetes, lupus, systemic sclerosis, hemoglobinopathy, or coagulopathy), were excluded from the main analysis and examined separately. Results There were 1,941,057 unique women who had 3,755,444 singleton pregnancies, followed up over 42,313,758 person-years. The median follow-up time was 20.7 years (interquartile range, 9.9–30.0 years). 13,032 women (0.7%) had at least 1 stillbirth. Women who had experienced at least 1 stillbirth had a greater risk of developing chronic kidney disease (adjusted hazard ratio, 1.26; 95% confidence interval, 1.09–1.45) and end-stage renal disease (adjusted hazard ratio, 2.25; 95% confidence interval, 1.55–3.25) compared with women who only had live births. These associations persisted after removing all stillbirths that occurred in the context of preeclampsia, and small for gestational age or congenital malformations (for chronic kidney disease, adjusted hazard ratio, 1.33; 95% confidence interval, 1.13–1.57; for end-stage renal disease, adjusted hazard ratio, 2.95; 95% confidence interval, CI 1.86–4.68). There was no significant association observed between stillbirth and either chronic kidney disease or end-stage renal disease in women who had preexisting medical comorbidities (chronic kidney disease, adjusted hazard ratio, 1.13; 95% confidence interval, 0.73–1.75 or end-stage renal disease, adjusted hazard ratio, 1.49; 95% confidence interval, 0.78–2.85). Conclusion Women who have a history of stillbirth may be at increased risk of chronic kidney disease and end-stage renal disease compared with women who have only had live births. This association persists independently of preeclampsia, and small for gestational age, maternal smoking, obesity, and medical comorbidities. Further research is required to determine whether affected women would benefit from closer surveillance and follow-up for future renal disease.

IntroductionAdverse pregnancy outcomes, such as hypertensive disorders of pregnancy (HDP), gestational diabetes (GDM) and preterm birth have been linked to maternal cardiovascular disease in later life. Pre-eclampsia (PE) is associated with an increased risk of postpartum microalbuminuria, but there is no clear consensus on whether HDP increases the risk of maternal chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Similarly, it is uncertain whether GDM, preterm birth and delivery of low birth-weight infants independently predict the risk of maternal renal disease in later life. The aims of this proposed systematic review and meta-analysis are to summarise the available evidence examining the association between adverse outcomes of pregnancy (HDP, GDM, preterm birth, delivery of low birth-weight infant) and later maternal renal disease and to synthesise the results of relevant studies.Methods and analysisA systematic search of PubMed, EMBASE and Web of Science will be undertaken using a detailed prespecified search strategy. Two authors will independently review the titles and abstracts of all studies, perform data extraction and appraise the quality of included studies using a bias classification tool. Original case–control and cohort studies published in English will be considered for inclusion. Primary outcomes of interest will be CKD and ESKD; secondary outcomes will be hospitalisation for renal disease and deaths from renal disease. Meta-analyses will be performed to calculate the overall pooled estimates using the generic inverse variance method. The systematic review will follow the Meta-analyses Of Observational Studies in Epidemiology guidelines.Ethics and disseminationThis systematic review and meta-analysis will be based on published data, and thus there is no requirement for ethics approval. The results will be shared through publication in a peer reviewed journal and through presentations at academic conferences.PROSPERO registration numberCRD42018110891

Objective. To describe the establishment of the fetoscopic guided laser occlusion (FLOC) technique for treatment of twin-to-twin transfusion syndrome (TTTS) and the initial results in a Swedish national center. Design. Retrospective, descriptive study. Setting. Tertiary level university hospital. Population. All referred and treated cases suffering significant TTTS. Methods. The present study includes all cases of FLOC for TTTS at the Center of Fetal Medicine at Karolinska University Hospital, Stockholm, Sweden from October 2001 until December 2009. Patients were referred from all over Sweden and a few from other Nordic countries. The patients were evaluated with ultrasound examination between gestational ages of 18 and 26 weeks. Data from patients were extracted from our electronic medical record system and, in addition, families were contacted and medical records requested from referring hospitals. Main outcome measures. Pregnancies with one or more surviving infants after FLOC treatment categorized according to stage of TTTS. Results. In 75% of pregnancies, one or more infant was born alive. At stage I, both infants survived in one pregnancy and one survived in the second. There was no significant difference between cases at stage II or III, i.e. 73 vs. 78% of pregnancies resulted in one or more surviving infant. At stage IV, 66% of pregnancies ended with one or more surviving infant. Conclusions. Treatment of TTTS is feasible in a rather small country like Sweden, with comparable results to other centers. There are strong arguments for centralization and further improvement of this kind of highly specialized treatment.

Objective. To generate a regression equation for the nuchal translucency (NT) median for the Swedish population and compare this with other median values. Setting. Eight Swedish hospitals. Sample. The data set included 20 887 unaffected fetuses. Methods. Calculation and generation of an NT centile chart for the Swedish population. Results. The NT centiles for crown-rump length (CRL) from 45 to 84mm were calculated and compared with the medians from Glasgow, from the Fetal Medicine Foundation (FMF, London, UK; FMF-original) and those published recently (FMF-new). The NT medians cease to increase at CRLs between 70 and 75mm. The Swedish, FMF-new and Glasgow medians followed the same pattern, but the Glasgow NT median curve was systematically lower by around 20%. Swedish, FMF-new and Glasgow medians differed in shape from the FMF-original medians, which continuously increase throughout the whole range of CRLs. Conclusions. Our results demonstrate that there are substantial differences in the NT medians and centiles between countries.

Introduction: We present a review of all cases of intravascular transfusions in red cell alloimmunization over a time span of 20 years in Stockholm. The aim of the study is to compare our results with published results from larger centers and to identify areas that can be further improved. Material and Methods: A retrospective cohort study was conducted of all women treated with intrauterine transfusions due to erythrocyte immunization in our hospital between June 1990 and June 2010. Primary outcome variables were fetal and neonatal survival, procedure-related complications and gestational age at delivery. Results: A total of 284 intrauterine transfusions were performed in 84 pregnancies, with an overall survival rate of 91.8%. Procedure-related and fatal complications occurred in the present study in 4.9 and 1.4% of fetuses or neonates, respectively. Procedure-related complications were significantly more common in free-loop transfusions than in transfusions in the intrahepatic part of the umbilical vein (OR: 5.4, p = 0.025). There was no significant difference between the intrahepatic and the placental cord insertion route (p = 0.83). Gestational age at first transfusion was significantly associated with an increased risk of a procedure-related complication (OR: 0.8, p = 0.019). Of the live-born infants, 24% of the neonates were born before gestational week 34. Discussion: Our study confirms previous studies demonstrating favorable results with intravascular transfusions.

This ex vivo study focuses on the mechanisms of endothelium-dependent dilatation in the uterine circulation of normal pregnancy (n = 12) and in women with preeclampsia (n = 12). Arteries (internal diameter, ∼250 μm) isolated by myometrial biopsy from women undergoing planned cesarean delivery or delivery as a result of the deterioration of preeclampsia were studied using a wire myograph. Bradykinin-induced dilatation was assessed in the presence and/or absence of pharmacological inhibitors to determine the contribution of nitric oxide and endothelium-derived hyperpolarizing factor (EDHF), as well as that of EDHF-mediated pathways such as myoendothelial gap junctions (MEGJs) and products of arachidonic acid, H(2)O(2) and cytochrome P450 2C9 (CYP2C9). Transmission electron microscopy was used to visualize morphological prerequisites for MEGJs. In normal pregnancy, EDHF through MEGJs appeared to be a predominant mediator conferring endothelium-dependent relaxation in small myometrial arteries. In preeclampsia, bradykinin-induced relaxation was reduced via compromised EDHF-type responses, in which the contribution of MEGJs became negligible. The attenuated role of MEGJs to endothelium-dependent relaxation was partly compensated through the contribution of H(2)O(2) or other endothelium-derived relaxing factors. CYP2C9 products of arachidonic acid had no effect on EDHF-type relaxation in arteries of women with normal pregnancy or with preeclampsia. We suggest that EDHF-type responses via MEGJs are primarily targeted in small myometrial arteries in women with preeclampsia. This could significantly contribute to the impaired uteroplacental blood flow in this disorder.

OBJECTIVE: To develop an indicator of maternal near miss as a proxy for maternal death and to study its association with maternalfactors and perinatal outcomes. METHODS: In a multicenter cross-sectional study, we collected maternal and perinatal data from the hospital records of a sample of women admitted for delivery over a period of two to three months in 120 hospitals located in eight Latin American countries. We followed a stratified multistage cluster random design. We assessed the intra-hospital occurrence of severe maternal morbidity and the latter's association with maternal characteristics and perinatal outcomes. FINDINGS: Of the 97 095 women studied, 2964 (34 per 1000) were at higher risk of dying in association with one or more of the following: being admitted to the intensive care unit (ICU), undergoing a hysterectomy, receiving a blood transfusion, suffering a cardiac or renal complication, or having eclampsia. Being older than 35 years, not having a partner, being a primipara or para > 3, and having had a Caesarean section in the previous pregnancy were factors independently associated with the occurrence of severe maternal morbidity. They were also positively associated with an increased occurrence of low and very low birth weight, stillbirth, early neonatal death, admission to the neonatal ICU, a prolonged maternal postpartum hospital stay and Caesarean section. CONCLUSION: Women who survive the serious conditions described could be pragmatically considered cases of maternal near miss. Interventions to reduce maternal and perinatal mortality should target women in these high-risk categories.

Cluster-based studies involving aggregate units such as hospitals or medical practices are increasingly being used in healthcare evaluation. An important characteristic of such studies is the presence of intracluster correlation, typically quantified by the intracluster correlation coefficient (ICC). Sample size calculations for cluster-based studies need to account for the ICC, or risk underestimating the sample size required to yield the desired levels of power and significance. In this article, we present values for ICCs that were obtained from data on 97,095 pregnancies and 98,072 births taking place in a representative sample of 120 hospitals in eight Latin American countries. We present ICCs for 86 variables measured on mothers and newborns from pregnancy to the time of hospital discharge, including 'process variables' representing actual medical care received for each mother and newborn. Process variables are of primary interest in the field of implementation research. We found that overall, ICCs ranged from a minimum of 0.0003 to a maximum of 0.563 (median 0.067). For maternal and newborn outcome variables, the median ICCs were 0.011 (interquartile range 0.007-0.037) and 0.054 (interquartile range 0.013-0.075) respectively; however, for process variables, the median was 0.161 (interquartile range 0.072-0.328). Thus, we confirm previous findings that process variables tend to have higher ICCs than outcome variables. We demonstrate that ICCs generally tend to increase with higher prevalences (close to 0.5). These results can help researchers calculate the required sample size for future research studies in maternal and perinatal health.

OBJECTIVE: To set up a global system for monitoring maternal and perinatal health in 54 countries worldwide. METHODS: The WHO Global Survey for Monitoring Maternal and Perinatal Health was implemented through a network of health institutions, selected using a stratified multistage cluster sampling design. Focused information on maternal and perinatal health was abstracted from hospital records and entered in a specially developed online data management system. Data were collected over a two- to three-month period in each institution. The project was coordinated by WHO and supported by WHO regional offices and country coordinators in Africa and the Americas. FINDINGS: The initial survey was implemented between September 2004 and March 2005 in the African and American regions. A total of 131 institutions in seven African countries and 119 institutions in eight Latin American countries participated. CONCLUSION: This project has created a technologically simple and scientifically sound system for large-scale data management, which can facilitate programme monitoring in countries.

We hypothesized that in preeclampsia (PE), contribution of endothelium-derived hyperpolarizing factor (EDHF) and the mechanism/s of its action differ from that in normal pregnancy (NP). We aimed to assess endothelial function and morphology in arteries from NP and PE with particular focus on EDHF. Arteries (≈200 μm) were dissected from subcutaneous fat biopsies obtained from women undergoing cesarean section. With the use of wire myography, responses to the endothelium-dependent agonist bradykinin (BK) were determined before and after inhibition of pathways relevant to EDHF activity. The overall responses to BK in arteries from PE ( n = 13) and NP ( n = 17) were similar. However, in PE, EDHF-mediated relaxation was reduced ( P < 0.05). All women within the PE group were divided into two subgroups: with more ( group 1) or less ( group 2) than 50% reduction of EDHF-typed responses after 18-α-glycyrrhetinic acid (an inhibitor of myoendothelial gap junctions, MEGJs). The division showed that 1) MEGJs are principally involved when the EDHF contribution is reduced; and 2) when the EDHF contribution is similar to that in NP, the H2O2 and/or cytochrome P-450 epoxygenase products of arachidonic acid (AA), along with MEGJs, confer EDHF-mediated relaxation. In contrast, MEGJs were the main pathway for EDHF in NP. The abundant presence of MEGJs in arteries from NP but deficiency of them in PE was observed using transmission electron microscopy. We conclude that PE is associated with heterogeneous contribution of EDHF, and the mechanism behind EDHF-typed responses is mediated either by MEGJs alone or in combination with H2O2 or cytochrome P-450 epoxygenase metabolites of AA.

Objective To investigate pregnancy outcome for fetuses with nuchal translucency (NT) ≥3.5 mm but normal karyotype in the Stockholm (Sweden) area. Methods A retrospective population-based cohort study. From 2006 to 2012, fetal NT was measured in 55123 singleton pregnancies. There were 341 pregnancies with NT thickness ≥3.5 mm; 139 had a normal karyotype, 164 had an abnormal karyotype and 38 were removed from the study. Pregnancy outcome was defined as adverse (termination of pregnancy [TOP], miscarriage [MC], intrauterine fetal death [IUFD], or delivery of a child with structural defects or genetic disorders), or favourable (delivery of a child without any structural defects or genetic disorders diagnosed before discharge). Results Of the 139 high NT pregnancies with normal karyotype, 110 (79.2%) resulted in live births, one (0.7%) IUFD, 23 (16.5%) TOP and five (3.6%) MC. The risk of an adverse pregnancy outcome increased with increasing NT. Structural fetal defects were found in 28 (19.5%) of pregnancies undergoing second trimester ultrasound screening, of which seven resulted in live births and 21 were terminated. The most common structural defect was cardiac defects. Conclusions Adverse pregnancy outcome increased with increasing NT, even with normal karyotype, however, the prognosis is good if the second trimester ultrasound screening is normal.

The objective was to study fetal growth parameters in in vitro fertilization (IVF) pregnancies and to investigate the relationship between fetal growth and maternal blood pressure.We examined 64 women, pregnant after in vitro fertilization, with repeated ultrasound examinations measuring biparietal diameter, femur length, abdominal diameter and fetal weight at 24, 30, and 36 weeks of gestation. We calculated deviations in percent from expected values in regards to biparietal diameter, femur length, abdominal diameter, and fetal weight. Blood pressure was measured every second week.Biparietal diameter in the study group was significantly smaller at 24 (-3.3%, 95%CI -4.4 to -2.2) and 30 (-1.4%; 95%CI -2.5% to -0.3) weeks. Femur length differed significantly on all three occasions, at 24 (-6.3%; 95%CI -7.7 to -5.1), 30 (-6.6%; 95%CI -8.0 to -5.3), and 36 (-3.9%; 95%CI; -5.0 to -2.8) weeks. Abdominal diameter demonstrated a significant deviation at 24 weeks (-1.6%; 95%CI -2.8 to -0.4). Fetal weight did not reach significant deviations at any gestational age. There was no correlation between deviation of the individual growth parameters or estimated fetal weight and elevated blood pressure.The growth pattern of in vitro fertilization pregnancies does not seem to differ from spontaneously conceived pregnancies to any appreciable extent. In the present material, no relationship between fetal growth and maternal blood pressure could be observed. We could not show that an impaired fetal growth predates the development of hypertension.

Objectives To determine the accuracy of established ultrasound dating formulae when used at 12-14 weeks of gestation. Methods One-hundred and sixty-seven singleton pregnancies conceived after in-vitro fertilization (IVF) underwent a dating scan at 12-14 weeks of gestation. Gestational age at the dating scan was calculated by adding 14 days to the number of days between the date of oocyte retrieval and the date of the ultrasound scan. Gestational age according to oocyte retrieval was regarded as the true gestational age. True gestational age was compared to gestational age calculated on the basis of 21 dating formulae based on fetal crown-rump length (CRL) measurements and to three dating formulae based on fetal biparietal diameter (BPD) measurements. In a previous study the three BPD formulae tested here had been shown to be superior to four other BPD formulae when used at 12-14 weeks of gestation. The mean of the differences between estimated and true gestational age and their standard deviation (SD) were calculated for each formula. The SD of the differences was assumed to reflect random measurement error. Systematic measurement error was assumed to exist if zero lay outside the mean difference ± 2SE (SE: standard error of the mean). Results The three best CRL formulae were associated with mean (non-systematic) measurement errors of -0.0, -0.1 and -0.3 days, and the SD of the measurement errors of these formulae varied from 2.37 to 2.45. All but two of the remaining CRL formulae were associated with systematic over- or under-estimation of gestational age, and the SDs of their measurement error varied between 2.25 and 4.86 days. Dating formulae using BPD systematically underestimated gestational age by -0.4 to -0.7 days, and the SDs of their measurement errors varied from 1.86 to 2.09. Conclusions We have identified three BPD formulae that are suitable for dating at 12-14 weeks of gestation. They are superior to all 21 CRL formulae tested here, because their random measurement errors were much smaller than those of the three best CRL formulae. The small systematic negative measurement errors associated with the BPD formulae are likely to be clinically unimportant. (Less)

Objectives Nuchal translucency (NT) screening increases antenatal detection of Down syndrome (DS) compared to maternal age-based screening. We wanted to determine if a change in policy for prenatal diagnosis would result in fewer babies born with DS. Methods A total of 39572 pregnant women were randomized to a scan at 12-14 gestational weeks including NT screening for DS (12-week group) or to a scan at 15-20 weeks with screening for DS based on maternal age (18-week group). Fetal karyotyping was offered if risk according to NT was >= 1 :250 in the 12-week group and if maternal age was >= 35 years in the 18-week group. Both policies included the offer of karyotyping in cases of fetal anomaly detected at any scan during pregnancy or when there was a history of fetal chromosomal anomaly. The number of babies born with DS and the number of invasive tests for fetal karyotyping were compared. Results Ten babies with DS were born alive with the 12-week policy vs. 16 with the 18-week policy (P = 0.25). More fetuses with DS were spontaneously lost or terminated in the 12-week group (45119 796) than in the 18-week group (27119 776; P = 0.04). All women except one with an antenatal diagnosis of DS at < 22 weeks terminated the pregnancy. For each case of DS detected at < 22 weeks in a living fetus there were 16 invasive tests in the 12-week group vs. 89 in the 18-week group. NT screening detected 71% of cases of DS for a 3.5% test-positive rate whereas maternal age had the potential of detecting 58% for a test-positive rate of 18%. Conclusions The number of newborns with DS differed less than expected between pregnancies that had been screened at 12-14 weeks' gestation by NT compared with those screened at IS-20 weeks by maternal age. One explanation could be that NT screening - because it is performed early in pregnancy - results in the detection and termination of many pregnancies with a fetus with DS that would have resulted in miscarriage without intervention, and also by many cases of DS being detected because of a fetal anomaly seen on an 18-week scan. The major advantage of the 1.2-week scan policy is that many fewer invasive tests for fetal karyotyping are needed per antenatally detected case of DS. (Less)

Objective. To evaluate the use of an Internet-based information system on infectious disorders (INFPREG) in antenatal care in Sweden. Methods. A postal questionnaire was sent to all antenatal clinics in Sweden in 2000 ( n = 515) and 2002 ( n = 503). The questionnaire consisted of sections covering use of computers, availability of Internet connections and the use of INFPREG in patient care. Results. We received 404 completed questionnaires in 2000 and 501 in 2002. In 2000, 81% of the midwives had access to computers at their antenatal clinics, and this number had increased to 93% in 2002. Sixty-eight percent and 88% in 2000 and 2002, respectively, had computers with an Internet connection. Of the responding midwives, 74% in 2000 and 84% in 2002 had received information concerning INFPREG. In 2000, 29% of the midwives had visited INFPREG and this figure had increased to 58% in 2002. Of the midwives that had used INFPREG, 67% in 2000 and 81% in 2002 reported that the information obtained from the site was i...

Introduction Studies on the association between pre-eclampsia and the risk of kidney disease in the women are limited. Objectives To examine the association between pre-eclampsia and the risk of end stage renal disease (ESRD) chronic kidney disease (CKD) after delivery. Patients and methods Using data from the Swedish Medical Birth Register, women who had singleton live birth in Sweden between January 1, 1982 and December 31, 2012 were identified. Pre-eclampsia, ESRD and CKD diagnoses based on the International Classification of Diseases, eighth, ninth and tenth revision were identified from the Swedish Medical Birth Register and the Swedish National Hospital Register respectively. We conducted Cox proportional hazards regression analysis to examine the association between pre-eclampsia and ESRD and CKD adjusting for several potential confounders including maternal age, body mass index, smoking, parity, country of birth, pre-pregnancy diabetes, pre-pregnancy hypertension, small for gestational age and large for gestational age. Results The study cohort consisted of 1,433,123 women giving birth to 2,789,313 singleton live babies in Sweden between January 1, 1982 and December 31, 2012. During the study period, 59,583 (4.2%) women having 82,591 singleton live births had pre-eclampsia, 1606 women (3134 pregnancies) had ESRD and 19,421 (32,049 pregnancies) had CKD. Including the entire study cohort, the findings supported an association between pre-eclampsia and ESRD in the crude (HR = 5.02, [95% CIs: 2.42–3.82]) and adjusted (HR = 2.72, [95% CIs: 2.34–3.20]) models and CKD in the crude (HR = 1.41; [95% CIs: 1.35–1.47]) and adjusted (HR = 1.44; [95% CIs: 1.38–1.50]) models. Women who had two pregnancies with pre-eclampsia had a 10-fold increased risk of ESRD in the crude analysis (HR = 10.13; [95% CIs: 6.76, 15.19]) and 3-fold increased risk of ESRD in the adjusted analysis (HR = 2.98; [95% CIs: 1.89, 4.70]). Conclusion The present findings suggest that women with pre-eclampsia are at 2 to 3-fold increased risk of ESRD and 40% increased risk of CKD compared to parous women with no pre-eclampsia. The association was significant across a range of subgroup analyses.

Lactate can safely and easily be determined in fetal scalp and umbilical artery blood with a new microvolume (5 microliters) lactate meter. Comparison between lactate and pH in scalp blood revealed a significant correlation (r = -0.43; P < .001). In a management trial where scalp lactate was compared to scalp pH, the lactate group underwent significantly more successful blood sampling procedures and fewer number of scalp incisions per blood sampling attempt. The mode of delivery and neonatal outcome were similar in patients managed with lactate and those using pH. Lactate concentration in umbilical artery blood had the same predictive properties as pH or base deficit in relation to poor neonatal outcome. Our data suggest that this method for lactate determination is robust and feasible and is suitable as a tool for fetal monitoring. Additional clinical management trials will be required to define the clinical usefulness of this method and how it should be combined with other modalities for fetal monitoring.

Objective: We investigated lactate concentrations in fetal scalp and cord blood to determine the sources of fetal lactacidosis in fetuses with ominous heart rate patterns. Methods: Cord blood was collected from newly delivered infants who had been monitored by fetal scalp blood sampling during labor. In 250 cases umbilical arterial and venous cord blood lactate levels were measured. We assessed the umbilical arterial lactate concentrations in relation to the venous lactate levels, the arterial pH level, base excess, and arteriovenous lactate differences in cord blood. In 103 cases the levels of lactate in fetal scalp blood, sampled within 60 minutes of delivery, were compared with those in the umbilical artery and vein and the pH level and base excess immediately after birth. Results: Lactate level in the umbilical artery showed a significant correlation to that in umbilical venous blood (r = .84, P < .001), to arteriovenous lactate differences (r = .52, P < .001), as well as to pH (r = −.55, P < .001) and base excess (r = −.63, P < .001) in arterial cord blood. Lactate concentrations in fetal scalp blood shortly before delivery showed a significant correlation to lactate levels in the umbilical arterial (r = .65, P < .001) and venous blood (r = .62, P < .001). Conclusion: The study indicates a close correlation between lactate levels in arterial and venous cord blood, as well as between the lactate levels and pH and base excess in cord arterial blood in patients with ominous fetal heart rate patterns. We also found an increased fetal contribution with increasing lactacidemia. Lactate concentrations in fetal scalp blood correlated well with those in cord arterial and venous blood.

Objective To study whether a routine with a routine ultrasound examination (routine scan) at 41 gestational weeks as compared with ultrasound on clinical indication (indicated scan), lowered the risk of severe adverse fetal outcome in post-term period. Design A retrospective cohort study. Setting Karolinska University Hospital, Stockholm, Sweden. Population Eight years of deliveries, 2002–2009. Method One of the two delivery units at Karolinska University Hospital used a routine scan at 41 week of gestation and the other unit used an indicated scan. Severe adverse fetal outcome were defined: severe asphyxia, death or cerebral damage. The study was analysed using logistic regression with adjustment for potential confounders. Main outcome measures Differences in post-term severe adverse fetal outcome. Results No increased risk of post-term severe adverse fetal outcome was seen at the unit using a routine scan; conversely, a 48% significantly increased risk was seen at the unit using an indicated scan (OR 0.89, 95% confidence interval, CI, 0.5–1.5 and OR 1.48, 95% CI 1.06–2.1, respectively). Comparing post-term periods, there was no significantly increased risk at the unit using indicated scans (OR 1.6, 95% CI 0.9–3.0). There was a 60% increased prevalence of small-for-gestational age (SGA) newborns in the post-term period at the unit using indicated scans (OR 1.6, 95% CI 1.1–2.4), but no differences in operative delivery. Conclusion A policy to use routine scans at 41 weeks of gestation seems to normalise an increased post-term risk of severe adverse fetal outcome, possible due to increased awareness of SGA and/or oligohydramniosis.

Objective To compare causes of stillbirth in preterm and term pregnancies. Design Cohort study. Setting All delivery wards in Stockholm, 1998–2009. Population Stillbirths from singleton pregnancies of gestational age ≥22+0 (n = 1089) extracted from a web-based database including all stillbirths in the major Stockholm area since 1998. Methods The parents of the stillborns were all offered an extensive standardized investigation. The causes of death were assigned in a perinatal audit using the Stockholm classification of stillbirth. Singleton stillbirths were divided into preterm (gestational week 22+0–36+6) and term/post-term (gestational week ≥37+0). The term/post-term group was subdivided into term (gestational week 37+0–40+6) and post-term stillbirths (gestational week ≥41+0). Main outcome measure Causes of stillbirth at different gestational ages. Results A higher proportion of placental abruption and preeclampsia/hypertension was seen in preterm stillbirths compared with term/post-term stillbirths, which instead had a higher proportion of umbilical cord complications and infection. Infection was more common in post-term than term stillbirths (46.5 vs. 19.8%, p

To compare the effect of endothelin on isolated resistance arteries from different vascular beds in normal and preeclamptic women before and after pretreatment with the ETA receptor antagonist BQ-123.Resistance arteries from myometrial and omental biopsies obtained at cesarean section of normal pregnant and preeclamptic women were dissected and mounted in organ baths for recording of isometric tension. The contractile response to endothelin-1 in presence and absence of BQ-123 was recorded.Endothelin-1 induced similar concentration-dependent contractions in all arteries investigated. In women with preeclampsia the contractile response induced by endothelin-1 was significantly higher in omental as compared to myometrial vessels. Pretreatment with BQ-123 significantly shifted the concentration-response curve to the right but only reduced the maximum contractile response in omental vessels.Endothelin-1 is a potent constrictor of resistance arteries from different vascular beds in normal pregnancy and preeclampsia. The contractile effect is at least in part mediated by ETA receptors, since it was significantly reduced after pretreatment with BQ-123. In preeclamptic but not in normal pregnant women the response to endothelin-1 was reduced in myometrial as compared to omental arteries, possibly secondary to receptor down regulation.