Risk factors for and pregnancy outcomes after SARS-CoV-2 in pregnancy according to disease severity: A nationwide cohort study with validation of the SARS-CoV-2 diagnosis.

INTRODUCTION: We identified risk factors and outcomes associated with SARS-CoV-2 infection in pregnancy in a universally tested population according to disease severity and validated information on SARS-CoV-2 during pregnancy in national health registers in Denmark. MATERIAL AND METHODS: Cohort study using data from national registers and medical records including all pregnancies between March 1, 2020 and February 28, 2021. We compared women with a validated positive SARS-CoV-2 test during pregnancy with non-infected pregnant women. Risk factors and pregnancy outcomes were assessed by Poisson and Cox regression models and stratified according to disease severity defined by hospital admission status and admission reason (COVID-19 symptoms or other). Using medical record data on actual period of pregnancy, we calculated predictive values of the SARS-CoV-2 diagnosis in pregnancy in the registers. RESULTS: SARS-CoV-2 infection was detected in 1819 (1.6%) of 111 185 pregnancies. Asthma was associated with infection (relative risk [RR] 1.63, 95% confidence interval [CI] 1.28-2.07). Risk factors for severe COVID-19 disease requiring hospital admission were high body mass index (median ratio 1.06, 95% CI 1.04-1.09), asthma (RR 7.47, 95% CI 3.51-15.90) and gestational age at the time of infection (gestational age 28-36 vs < 22: RR 3.53, 95% CI 1.75-7.10). SARS-CoV-2-infected women more frequently had hypertensive disorders in pregnancy (adjusted hazard ratio [aHR] 1.31, 95% CI 1.04-1.64), early pregnancy loss (aHR 1.37, 95% CI 1.00-1.88), preterm delivery before gestational age 28 (aHR 2.31, 95% CI 1.01-5.26), iatrogenically preterm delivery before gestational age 37 (aHR 1.49, 95% CI 1.01-2.19) and small-for-gestational age children (aHR 1.28, 95% CI 1.05-1.54). The associations were stronger among women admitted to hospital for any reason. The validity of the SARS-CoV-2 diagnosis in relation to pregnancy in the registers compared with medical records showed a negative predictive value of 99.9 (95% CI 99.9-100.0) and a positive predictive value of 82.1 (95% CI 80.4-83.7). CONCLUSIONS: Women infected with SARS-CoV-2 during pregnancy were at increased risk of hypertensive disorders in pregnancy, early pregnancy loss, preterm delivery and having children small for gestational age. The validity of Danish national registers was acceptable for identification of SARS-CoV-2 infection during pregnancy.

Prevalence and severity of diabetic retinopathy in pregnant women with diabetes-time to individualize photo screening frequency.

AIMS: To evaluate the prevalence and severity of diabetic retinopathy including macular oedema in pregnant women with diabetes and to identify women in whom the frequency of retinal screening can be reduced to minimize the burden of health care visits. METHODS: A cohort study of 348 women with pre-existing diabetes were routinely screened with retinal photo in early (12 weeks) and late pregnancy (27 weeks). Diabetic retinopathy was classified in five stages in accordance with National Danish Guidelines based on the eye with the highest retinopathy level. Sight-threatening retinopathy was defined as the presence of proliferative retinopathy and/or clinically significant macular oedema (CSMO). RESULTS: Retinopathy was present in 52% (116/223) vs. 14% (17/125), with sight-threatening retinopathy in 16% (35/223) vs. 6% (7/125) of women with type 1 and type 2, respectively. Women without retinopathy in early and late pregnancy were characterized by shorter diabetes duration (p < 0.0001 and p = 0.008) and predominance of type 2 diabetes. Amongst the 50% (175/348) of the cohort having no retinopathy in early pregnancy and HbA1c<53 mmol/mol (7.0%), none developed sight-threatening retinopathy and 94% (165/175) remained without any retinopathy during pregnancy. Development of sight-threatening retinopathy was mainly observed in women with retinopathy in early pregnancy. Treatment for sight-threatening retinopathy was given to a minority (2.7 and 2.4%, respectively). CONCLUSION: Good glycaemic control and no retinopathy was seen in a large proportion of women in early pregnancy and none of these women developed sight-threatening retinopathy. The frequency of retinal screening can probably be safely reduced during pregnancy in these women.

The impact of anti-hypertensive treatment on foetal growth and haemodynamics in pregnant women with pre-existing diabetes - An explorative study.

OBJECTIVES: To explore the impact of anti-hypertensive treatment of pregnancy-induced hypertension on foetal growth and hemodynamics in women with pre-existing diabetes. METHODS: A prospective cohort study of 247 consecutive pregnant women with pre-existing diabetes (152 type 1 diabetes; 95 type 2 diabetes), where tight anti-hypertensive treatment was initiated and intensified (mainly with methyldopa) when office blood pressure (BP) ≥135/85 mmHg and home BP ≥130/80 mmHg. Foetal growth was assessed by ultrasound at 27, 33 and 36 weeks and foetal hemodynamics were assessed by ultrasound Doppler before and 1-2 weeks after initiation of anti-hypertensive treatment. RESULTS: In 215 initially normotensive women, anti-hypertensive treatment for pregnancy-induced hypertensive disorders was initiated in 42 (20%), whilst 173 were left untreated. Chronic hypertension was present in 32 (13%). Anti-hypertensive treatment for pregnancy-induced hypertensive disorders was not associated with foetal growth deviation (linear mixed model, p = 0.681). At 27 weeks, mainly before initiation of anti-hypertensive treatment, the prevalence of small foetuses with an estimated foetal weight <10th percentile was 12% in women initiating anti-hypertensive treatment compared with 4% in untreated women (p = 0.054). These numbers were close to the prevalence of birth weight ≤10th percentile (small for gestational age (SGA)) (17% vs. 4%, p = 0.003). Pulsatility index in the umbilical and middle cerebral artery remained stable after the onset of anti-hypertensive treatment in a representative subgroup (n = 12, p = 0.941 and p = 0.799, respectively). CONCLUSION: There is no clear indication that antihypertensive treatment causes harm in this particular at-high-risk group of pregnant women with diabetes, such that a larger well-designed study to determine the value of tight antihypertensive control would be worthwhile.

Potentially modifiable risk factors of preterm delivery in women with type 1 and type 2 diabetes.

AIMS/HYPOTHESIS: We aimed to identify potentially modifiable risk factors and causes for preterm delivery in women with type 1 or type 2 (pre-existing) diabetes. METHODS: A secondary analysis of a prospective cohort study of 203 women with pre-existing diabetes (117 type 1 and 86 type 2 diabetes) was performed. Consecutive singleton pregnancies were included at the first antenatal visit between September 2015 and February 2018. RESULTS: In total, 27% (n = 55) of the 203 women delivered preterm at median 36 + 0 weeks. When stratified by diabetes type, 33% of women with type 1 diabetes delivered preterm compared with 20% in women with type 2 diabetes (p = 0.04). Women delivering preterm were characterised by a higher prevalence of pre-existing kidney involvement (microalbuminuria or diabetic nephropathy) (16% vs 3%, p = 0.002), preeclampsia (26% vs 5%, p < 0.001), higher positive ultrasound estimated fetal weight deviation at 27 gestational weeks (2.7% vs -1.6% from the mean, p = 0.008), higher gestational weight gain (399 g/week vs 329 g/week, p = 0.01) and similar HbA1c levels in early pregnancy (51 mmol/mol [6.8%] vs 49 [6.6%], p = 0.22) when compared with women delivering at term. Independent risk factors for preterm delivery were pre-existing kidney involvement (OR 12.71 [95% CI 3.0, 53.79]), higher gestational weight gain (per 100 g/week, OR 1.25 [1.02, 1.54]), higher positive ultrasound estimated fetal weight deviation at 27 gestational weeks (% from the mean, OR 1.07 [1.03, 1.12]) and preeclampsia (OR 7.04 [2.34, 21.19]). Two-thirds of preterm deliveries were indicated and one-third were spontaneous. Several contributing factors to indicated preterm delivery were often present in each woman. The main indications were suspected fetal asphyxia (45%), hypertensive disorders (34%), fetal overgrowth (13%) and maternal indications (8%). Suspected fetal asphyxia mainly included falling insulin requirement and abnormal fetal haemodynamics. CONCLUSIONS/INTERPRETATIONS: Presence of preeclampsia, higher positive ultrasound estimated fetal weight deviation at 27 gestational weeks and higher gestational weight gain were independent potentially modifiable risk factors for preterm delivery in this cohort of women with pre-existing diabetes. Indicated preterm delivery was common with suspected fetal asphyxia or preeclampsia as the most prevalent causes. Prospective studies evaluating whether modifying these predictors will reduce the prevalence of preterm delivery are warranted.

Prevalence of anxiety and depression symptoms in pregnant women with type 2 diabetes and the impact on glycaemic control.

AIMS: To study the prevalence of anxiety and depression symptoms in pregnant women with type 2 diabetes compared with pregnant women without diabetes. Secondly, to explore whether anxiety and/or depression symptoms in early pregnancy have an impact on glycaemic control and gestational weight gain. METHODS: A prospective cohort study of 90 consecutive singleton pregnant women with type 2 diabetes and 88 singleton pregnant women without diabetes. All women completed the Hospital Anxiety and Depression Scale questionnaire in early and late pregnancy. A score ≥8 in the anxiety or the depression scale was used to define anxiety and/or depression symptoms. RESULTS: Anxiety and/or depression symptoms were present in 40% of women with type 2 diabetes and 7% of women without diabetes in early pregnancy (Relative Risk = 5.87 (95% Confidence Interval: 2.60-13.22)). The figures were similar in late pregnancy. In women with type 2 diabetes and anxiety and/or depression symptoms in early pregnancy, HbA1c (mean ± SD) was 52 ± 14 vs. 49 ± 11 mmol/mol (6.9 ± 1.2 vs. 6.6 ± 1.0%), p = 0.31 in early pregnancy and 43 ± 8 vs. 40 ± 4 mmol/mol (6.1 ± 0.7 vs. 5.8 ± 0.4%), p = 0.04 in late pregnancy compared with women without symptoms. Gestational weight gain was similar in both groups. CONCLUSIONS: In women with type 2 diabetes, 40% had anxiety and/or depression symptoms in early pregnancy. Women with these symptoms obtained less optimal glycaemic control in late pregnancy but similar gestational weight gain as the remaining women.

SARS-CoV-2 infection in pregnancy in Denmark-characteristics and outcomes after confirmed infection in pregnancy: A nationwide, prospective, population-based cohort study.

INTRODUCTION: Assessing the risk factors for and consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy is essential to guide clinical care. Previous studies on SARS-CoV-2 infection in pregnancy have been among hospitalized patients, which may have exaggerated risk estimates of severe outcomes because all cases of SARS-CoV-2 infection in the pregnant population were not included. The objectives of this study were to identify risk factors for and outcomes after SARS-CoV-2 infection in pregnancy independent of severity of infection in a universally tested population, and to identify risk factors for and outcomes after severe infection requiring hospital admission. MATERIAL AND METHODS: This was a prospective population-based cohort study in Denmark using data from the Danish National Patient Register and Danish Microbiology Database and prospectively registered data from medical records. We included all pregnancies between March 1 and October 31, 2020 and compared women with a positive SARS-CoV-2 test during pregnancy to non-infected pregnant women. Cases of SARS-CoV-2 infection in pregnancy were both identified prospectively and through register linkage to ensure that all cases were identified and that cases were pregnant during infection. Main outcome measures were pregnancy, delivery, maternal, and neonatal outcomes. Severe infection was defined as hospital admission due to coronavirus disease 2019 (COVID-19) symptoms. RESULTS: Among 82 682 pregnancies, 418 women had SARS-CoV-2 infection during pregnancy, corresponding to an incidence of 5.1 per 1000 pregnancies, 23 (5.5%) of which required hospital admission due to COVID-19. Risk factors for infection were asthma (odds ratio [OR] 2.19, 95% CI 1.41-3.41) and being foreign born (OR 2.12, 95% CI 1.70-2.64). Risk factors for hospital admission due to COVID-19 included obesity (OR 2.74, 95% CI 1.00-7.51), smoking (OR 4.69, 95% CI 1.58-13.90), infection after gestational age (GA) 22 weeks (GA 22-27 weeks: OR 3.77, 95% CI 1.16-12.29; GA 28-36 weeks: OR 4.76, 95% CI 1.60-14.12), and having asthma (OR 4.53, 95% CI 1.39-14.79). We found no difference in any obstetrical or neonatal outcomes. CONCLUSIONS: Only 1 in 20 women with SARS-CoV-2 infection during pregnancy required admission to hospital due to COVID-19. Risk factors for admission comprised obesity, smoking, asthma, and infection after GA 22 weeks. Severe adverse outcomes of SARS-CoV-2 infection in pregnancy were rare.

White coat hypertension in early pregnancy in women with pre-existing diabetes: prevalence and pregnancy outcomes.

AIMS/HYPOTHESIS: Hypertensive disorders are prevalent among pregnant women with pre-existing diabetes, but the prevalence and impact of white coat hypertension are unknown. Measurement of home BP before initiation of antihypertensive treatment is necessary to identify white coat hypertension since international guidelines recommend that white coat hypertension is left untreated. The aim of this study, conducted among women with pre-existing diabetes, was therefore to examine the prevalence of white coat hypertension in early pregnancy, and pregnancy outcome in women with white coat hypertension in early pregnancy. METHODS: A prospective cohort study was undertaken involving women with pre-existing diabetes from a geographically well-defined area. Based on office BP in early pregnancy and home BP measured for 3 days, women were categorised in three groups: (1) white coat hypertension, defined as office BP ≥ 135/85 mmHg and mean home BP < 130/80 mmHg; (2) chronic hypertension, defined as pre-pregnancy hypertension including newly detected office BP ≥ 135/85 mmHg with home BP ≥ 130/80 mmHg; and (3) normotension. Office BP was measured every 2 weeks and, if ≥ 135/85 mmHg, home BP measurements were performed. White coat hypertension was left untreated, and tight antihypertensive treatment was initiated when both office BP ≥ 135/85 mmHg and home BP ≥ 130/80 mmHg. Pregnancy-induced hypertensive disorders were defined as office BP ≥ 140/90 mmHg with home BP ≥ 130/80 mmHg when available, with onset after 20 weeks of gestation. RESULTS: In total, 32 out of 222 women with pre-existing diabetes had newly detected office BP ≥ 135/85 mmHg in early pregnancy. White coat hypertension was present in 84% (27/32) of these women, representing 12% (95% CI 8%, 17%) of the whole cohort. Chronic hypertension was present in 14% (n = 32) and normotension in 74% (n = 163). Women with white coat hypertension were characterised by higher pre-pregnancy BMI (p = 0.011), higher home BP (p < 0.001) and higher prevalence of type 2 diabetes (p = 0.009), but similar HbA1c (p = 0.409) compared to women with normotension. Regarding pregnancy outcome, pregnancy-induced hypertensive disorders developed in 44% (12/27) of women with white coat hypertension in comparison with 22% (36/163) among initially normotensive women (p = 0.013), while the prevalence of preterm delivery was comparable (p = 0.143). The adjusted analysis, performed post hoc, suggested approximately double the risk of developing pregnancy-induced hypertensive disorders (OR 2.43 [CI 0.98, 6.05]) if white coat hypertension was present in early pregnancy, independently of pre-pregnancy BMI and parity. CONCLUSIONS/INTERPRETATION: White coat hypertension is prevalent in women with pre-existing diabetes and may indicate a high risk of later development of pregnancy-induced hypertensive disorders. To distinguish between persistent white coat hypertension and onset of pregnancy-induced hypertension, repeated home BP monitoring is recommended when elevated office BP is detected. The study was registered at ClinicalTrials.gov (ID: NCT02890836).

An audit on a routine antenatal nonstress testing program in pregnant women with preexisting diabetes.

INTRODUCTION: The objective was to evaluate the effectiveness of routine (planned) antenatal nonstress tests (NSTs) in pregnant women with preexisting diabetes. MATERIAL AND METHODS: A retrospective single-center study of 642 consecutive pregnancies in women with preexisting diabetes who gave birth to a singleton ≥22 weeks. Weekly planned NSTs were commenced at 33-35 weeks. In pregnancies with maternal-fetal complications, the initiation and frequency of the planned NST were individualized. Daily maternal assessment of fetal activity was recommended from 28 weeks, and decreased fetal activity indicated an unplanned NST. Data were collected from medical records, and local and regional databases. RESULTS: In total, 3016 planned NSTs were performed, with a median of five (range 0-12) tests per pregnancy. Ninety-five planned NSTs (3.1%) were abnormal, a finding confirmed by retesting the same day in eight cases (8.4%), thus leading to delivery. Complications were present in seven of these eight pregnancies, whereas no fetal movements for the last 3 days were reported when the planned NST was performed in the eighth pregnancy. When specifically asked, five of the eight women stated that they had observed decreased fetal activity preceding the planned NST. In 86 pregnancies (13.4%), maternal perception of decreased fetal activity indicated in total 127 unplanned NSTs. The combination of decreased fetal activity and further obstetrical assessment led to delivery in 10 of these pregnancies (11.6%). One stillbirth occurred at 37 weeks in a pregnancy complicated by fetal achondroplasia and polyhydramnios, where the weekly planned NSTs had been normal. The overall stillbirth rate was thus 1.6/1000. CONCLUSIONS: Routine use of planned antenatal NSTs does not appear to be indicated in pregnancies in women with preexisting diabetes in the absence of maternal-fetal complications.

Vitamin D insufficiency, preterm delivery and preeclampsia in women with type 1 diabetes - an observational study.

INTRODUCTION: The aim of this study was to evaluate whether vitamin D insufficiency is associated with preterm delivery and preeclampsia in women with type 1 diabetes. MATERIAL AND METHODS: An observational study of 198 pregnant women with type 1 diabetes. 25-Hydroxy-Vitamin D and HbA1c were measured in blood samples in early (median 8 weeks, range 5-14) and late (34 weeks, range 32-36) pregnancy. Kidney involvement (microalbuminuria or nephropathy) at inclusion, smoking status at inclusion, preterm delivery (<37 weeks) and preeclampsia (blood pressure ≥140/90 mmHg and proteinuria) were registered. Vitamin D supplementation of 10 µg daily was routinely recommended. RESULTS: Thirty-nine (20%) of the 198 women delivered preterm and 16 (8%) developed preeclampsia. Vitamin D insufficiency (<50 nmol/L) was present in 68 women (34%) in early pregnancy and in 73 women (37%) in late pregnancy. Preterm delivery occurred more frequently in women with vitamin D insufficiency in late pregnancy (27% vs. 15%, crude odds ratio 2.1; 95% confidence interval 1.0-4.3, p = 0.04). After adjustment for preexisting kidney involvement, HbA1c in late pregnancy and smoking the association became nonsignificant (adjusted odds ratio 1.8; 95% confidence interval 0.8-3.7). Preeclampsia developed in 11% of women with vitamin D insufficiency vs. 6% of the remaining women (crude odds ratio 1.8; 95% confidence interval 0.9-4.1, p = 0.25). CONCLUSION: In women with type 1 diabetes, preterm delivery was twice as frequent in women with vitamin D insufficiency in late pregnancy in crude analysis, but in this small study, low vitamin D was not independently associated with preterm birth or preeclampsia.

Birth weight and its relation with medical nutrition therapy in gestational diabetes.

PURPOSE: The cornerstone in treatment of gestational diabetes mellitus (GDM) is medical nutrition therapy (MNT), but the effect on birth weight is disputed. The birth weight was evaluated with respect to length of MNT and adherence to diet. METHODS: We performed a cohort study on 436 women with GDM and 254 non-diabetic women. Women with a normal oral glucose tolerance test were included as controls as they had similar background predisposition as the women with GDM. The GDM women were subdivided according to MNT and the nutritional status was further stratified according to adherence to the current dietary guidelines. RESULTS: Birth weight above 4 kg was more prevalent in the non-diabetic women compared to the diet-treated GDM women (27 vs. 18%, p = 0.012) but similar to the GDM women who had no MNT (24%). Lower birth weight was associated with longer duration of MNT (r = -0.13, p = 0.021). The birth weight was 1.2 g lower per day of treatment. CONCLUSIONS: Medical nutrition therapy was associated with reduction of the fetal weight in women with GDM and the weight decreases with length of treatment. Birth weight above 4 kg was as prominent in the non-diabetic women as in the women with GDM without MNT.

Diabetic Nephropathy in Women With Preexisting Diabetes: From Pregnancy Planning to Breastfeeding.

In women with preexisting diabetes and nephropathy or microalbuminuria, it is important to deliver careful preconception counselling to assess the risk for the mother and the foetus, for optimizing glycaemic status and to adjust medical treatment. If serum creatinine is normal in early pregnancy, kidney function is often preserved during pregnancy, but complications such as severe preeclampsia and preterm delivery are still common. Perinatal mortality is now comparable with that in women with diabetes and normal kidney function. Besides strict glycaemic control before and during pregnancy, early and intensive antihypertensive treatment is important to optimize pregnancy outcomes. Methyldopa, labetalol, nifedipine and diltiazem are considered safe, whereas angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers should be stopped before or at confirmation of pregnancy. Supplementation with folic acid in early pregnancy and low-dose aspirin from 10 to 12 weeks reduces the risk of adverse pregnancy outcomes. During breastfeeding, several ACE inhibitors are considered safe.

Prediction and prevention of preeclampsia in women with preexisting diabetes: the role of home blood pressure, physical activity, and aspirin.

Women with type 1 or type 2 (preexisting) diabetes are four times more likely to develop preeclampsia compared with women without diabetes. Preeclampsia affects 9%-20% of pregnant women with type 1 diabetes and 7%-14% of pregnant women with type 2 diabetes. The aim of this narrative review is to investigate the role of blood pressure (BP) monitoring, physical activity, and prophylactic aspirin to reduce the prevalence of preeclampsia and to improve pregnancy outcome in women with preexisting diabetes. Home BP and office BP in early pregnancy are positively associated with development of preeclampsia, and home BP and office BP are comparable for the prediction of preeclampsia in women with preexisting diabetes. However, home BP is lower than office BP, and the difference is greater with increasing office BP. Daily physical activity is recommended during pregnancy, and limiting sedentary behavior may be beneficial to prevent preeclampsia. White coat hypertension in early pregnancy is not a clinically benign condition but is associated with an elevated risk of developing preeclampsia. This renders the current strategy of leaving white coat hypertension untreated debatable. A beneficial preventive effect of initiating low-dose aspirin (150 mg/day) for all in early pregnancy has not been demonstrated in women with preexisting diabetes.

Home Blood Pressure for the Prediction of Preeclampsia in Women With Preexisting Diabetes.

CONTEXT: Outside of pregnancy, home blood pressure (BP) has been shown to be superior to office BP for predicting cardiovascular outcomes. OBJECTIVE: This work aimed to evaluate home BP as a predictor of preeclampsia in comparison with office BP in pregnant women with preexisting diabetes. METHODS: A prospective cohort study was conducted of 404 pregnant women with preexisting diabetes; home BP and office BP were measured in early (9 weeks) and late pregnancy (35 weeks). Discriminative performance of home BP and office BP for prediction of preeclampsia was assessed by area under the receiver operating characteristic curves (AUC). RESULTS: In total 12% (n = 49/404) developed preeclampsia. Both home BP and office BP in early pregnancy were positively associated with the development of preeclampsia (adjusted odds ratio (95% CI) per 5 mm Hg, systolic/diastolic): home BP 1.43 (1.21-1.70)/1.74 (1.34-2.25) and office BP 1.22 (1.06-1.40)/1.52 (1.23-1.87). The discriminative performance for prediction of preeclampsia was similar for early-pregnancy home BP and office BP (systolic, AUC 69.3 [61.3-77.2] vs 64.1 [55.5-72.8]; P = .21 and diastolic, AUC 68.6 [60.2-77.0] vs 66.6 [58.2-75.1]; P = .64). Similar results were seen when comparing AUCs in late pregnancy (n = 304). In early and late pregnancy home BP was lower than office BP (early pregnancy P < .0001 and late pregnancy P < .01 for both systolic and diastolic BP), and the difference was greater with increasing office BP. CONCLUSION: In women with preexisting diabetes, home BP and office BP were positively associated with the development of preeclampsia, and for the prediction of preeclampsia home BP and office BP were comparable.

Falling Insulin Requirement in Pregnant Women With Diabetes Delivering Preterm: Prevalence, Predictors, and Consequences.

CONTEXT: Falling insulin requirements often lead to considerations of whether a pregnancy can continue safely or if delivery is indicated. OBJECTIVE: To evaluate prevalence and predictors of falling insulin requirements in pregnant women with preexisting diabetes delivering preterm and to explore the relationship to fetal asphyxia and neonatal morbidity. METHODS: A prospective cohort study of 101 consecutive singleton pregnant women with preexisting diabetes delivering preterm < 37 weeks (68 type 1 and 33 type 2 diabetes) where the prevalence of falling insulin requirements (≥20%) before delivery was recorded. RESULTS: In total, 27% (27/101) experienced falling insulin requirements of median 30% (interquartile range 24-40) before delivery. In all women with type 1 diabetes, the prevalence was 37% (25/68), whereas it was 43% (24/56) in those with indicated preterm delivery and 6% (2/33) among women with type 2 diabetes. In women with type 1 diabetes and indicated preterm delivery, falling insulin requirements were first identified at 34 + 5 (33 + 6-35 + 4) weeks + days and delivery occurred 3 (1-9) days later. Gestational age at delivery, prevalence of suspected fetal asphyxia, and neonatal morbidity were similar in women with and without falling insulin requirements. Neither glycemic control, nausea, or preeclampsia was associated with falling insulin requirement. CONCLUSION: Falling insulin requirements often preceded preterm delivery in women with type 1 diabetes, foremost when preterm delivery was indicated, but was not related to fetal asphyxia or neonatal morbidity. Whether falling insulin requirements in late pregnancy are a warning sign of placental insufficiency or mainly reflects variations in normal physiology needs further investigation.

Unchanged Prevalence of Preeclampsia After Implementation of Prophylactic Aspirin for All Pregnant Women With Preexisting Diabetes: A Prospective Cohort Study.

OBJECTIVE: To evaluate the prevalence of preeclampsia after implementation of prophylactic aspirin for all pregnant women with preexisting diabetes compared with the prevalence in a previous risk-based prophylaxis. RESEARCH DESIGN AND METHODS: A prospective observational cohort study of 410 consecutive pregnant women with preexisting diabetes categorized according to aspirin prophylaxis strategy, with the prevalence of preeclampsia as primary outcome. In total, 207 women were included after implementation of prophylactic aspirin for all pregnant women with preexisting diabetes in February 2018 (all-cohort). The 203 women included before this date, where aspirin prophylaxis was risk based and only prescribed to selected women (selected-cohort), were studied for comparison. RESULTS: Aspirin was prescribed at ∼10 gestational weeks for 88% (all-cohort) compared with 25% (selected-cohort). HbA1c, parity, chronic hypertension, home blood pressure, microalbuminuria/diabetic nephropathy, and smoking were similar in the two cohorts in early pregnancy. In the all-cohort, fewer women had type 2 diabetes (32% vs. 42%, respectively; P = 0.04) and BMI tended to be lower (P = 0.05). The prevalence of preeclampsia was similar (12% vs. 11%, P = 0.69) in the two cohorts, and this was also the case with stratification for diabetes type. Prevalence of preterm delivery <37 weeks (23% vs. 27%, P = 0.30), preterm preeclampsia (7% vs. 7%, P = 0.96), and infants large (40% vs. 32%, P = 0.07) and small (7% vs. 6%, P = 0.88) for gestational age was similar in the two cohorts. CONCLUSIONS: Implementation of prophylactic aspirin for all pregnant women with diabetes did not reduce the prevalence of preeclampsia compared with the previous risk-based prophylaxis in this cohort study.

Predictors of emergency cesarean section in women with preexisting diabetes.

OBJECTIVE: Preexisting diabetes in pregnancy is associated with a high risk of emergency cesarean section (CS), which is associated with increased risk of maternal and neonatal complications. Thus, the aim of this study was to identify possible predictors of emergency CS in women with preexisting diabetes. STUDY DESIGN: This is a secondary analysis of a prospective observational study of 204 women with preexisting diabetes (118 with type 1 diabetes and 86 with type 2) with singleton pregnancies recruited at Rigshospitalet, Copenhagen, Denmark from August 2015 to February 2018. Mode of delivery (trial of labor or planned CS) was individually planned in late pregnancy based on clinical variables reflecting maternal and fetal health including glycemic control and ultrasonically estimated fetal weight. Univariate and multivariable analyses were performed to identify possible predictors of in labor emergency CS. RESULTS: Trial of labor was planned in 79 % (n = 162) of the women of whom 65 % (n = 105) were delivered vaginally and 35 % (n = 57) by an emergency CS, while the remaining 21 % (n = 42) were offered a planned CS. Nulliparity (adjusted odds ratio (aOR) 5.6 95 % CI 1.7-18.8), presence of a hypertensive disorder (aOR 2.8, 95 % CI 1.2-6.7) and previous CS (aOR 6.7, 95 % CI 1.5-28.9) were independently associated with an emergency CS. Maternal height was inversely associated with emergency CS (aOR 0.6 95 %, CI 0.5-0.9 per 5 cm decrease). Neither maternal HbA1c nor ultrasonically estimated fetal size in late pregnancy were associated with emergency CS. Women scheduled for a planned CS were characterized by poorer glycemic control and higher estimated fetal size than those offered a trial of labor. CONCLUSION: Nulliparity, presence of a hypertensive disorder, previous CS and shorter maternal height were predictors of emergency CS in women with a planned trial of labor, whereas this not was the case for late pregnancy maternal Hba1c or fetal size estimated by ultrasound.

Routine use of antenatal nonstress tests in pregnant women with diabetes-What is the practice?

OBJECTIVE: Pregnancies complicated by maternal preexisting diabetes have a 4-5-fold increased risk of stillbirth, and consequently routine antenatal nonstress testing (NST) was implemented into clinical practice decades ago. Though, international guidelines lack consensus and recommend anything from twice weekly testing from 32 weeks to once weekly testing from 38 weeks. The objective of this study was to examine how routine antenatal NST was used in centers with specific interest and dedication in the care of pregnant women with preexisting diabetes. STUDY DESIGN: An electronic survey concerning the routine use of antenatal NST was sent to members of the European Diabetic Pregnancy Study Group (DPSG) between October 2016 and January 2017, representing in total 55 centers in 26 countries taking care of pregnant women with diabetes. RESULTS: Answers from 38 centers (69.1 % (38/55)) in 22 countries were received. Based on real world information from these primarily European centers, anything from avoiding routine antenatal NST to testing twice weekly from early in third trimester in women with preexisting diabetes was reported. NST was commonly used (71.1 % of centers) if insulin treatment was needed. NST was also used among diet treated women with type 2 diabetes in several places. The use varied markedly within and between countries. The most common practice was routine NST once weekly from 32 weeks. CONCLUSION: Among pregnant women with preexisting diabetes, routine antenatal testing practice with NST differs considerably both within and between countries. Studies examining the cost benefit of routine antenatal NST in pregnancies in women with the different types of diabetes are needed.

Physical activity, sedentary behavior and development of preeclampsia in women with preexisting diabetes.

AIMS: To explore the association between physical activity in early pregnancy and development of preeclampsia in women with preexisting diabetes. METHODS: In a prospective cohort study of 189 women with preexisting diabetes (110 type 1 and 79 type 2 diabetes), physical activity during pregnancy including sedentary behavior was evaluated with the Pregnancy Physical Activity Questionnaire. Primary outcome was preeclampsia. Secondary outcomes were preterm delivery, large and small for gestational age infants. RESULTS: Women developing preeclampsia (n = 23) had higher diastolic blood pressure in early pregnancy (mean 82 ± 9 SD vs. 77 ± 8, p = 0.004) and were more often nulliparous (91 vs. 52%, p < 0.001) compared with the remaining women (n = 166). Total physical activity in early pregnancy was similar between the groups (median 148 metabolic equivalent of task hours per week (MET-h/week) (interquartile range 118-227) versus 153 (121-205), p = 0.97). In early pregnancy, women developing preeclampsia reported a higher level of sedentary behavior (15 MET-h/week (7-18) versus 7 (4-15); p = 0.04); however, when adjusting for parity, diastolic blood pressure and smoking, the association attenuated (p = 0.13). Total physical activity and sedentary behavior in early pregnancy were not associated with preterm delivery, large or small for gestational age infants. CONCLUSIONS: Among women with diabetes, sedentary behavior was reported higher in early pregnancy in women developing preeclampsia compared with the remaining women, while total physical activity was similar. Sedentary behavior was a predictor of preeclampsia in the univariate analysis, but not in the multiple regression analysis, and larger studies are needed to evaluate this possible modifiable risk factor. Trial registration The study was registered at ClinicalTrials.gov (ID: NCT02890836).

Treatment with the long-acting insulin analog degludec during pregnancy in women with type 1 diabetes: An observational study of 22 cases.

AIM: To report glycemic control and pregnancy outcome in pregnant women with type 1 diabetes on insulin degludec. METHODS: Twenty-two women with type 1 diabetes on degludec from conception to delivery between 2014 and 2018 were compared with 51 pregnant women with type 1 diabetes on glargine. RESULTS: Baseline characteristics were comparable, however HbA1c was higher at median 9 (range 5-19) weeks in women on degludec compared to women on glargine (6.9% (5.7-8.7); (52 (39-72) mmol/mol) versus 6.4% (5.1-10.1); (46 (32-87) mmol/mol), p = 0.04). HbA1c was similar in late pregnancy (6.3% (5.6-7.1); (45 (38-54) mmol/mol) versus 6.1% (5.2-9.0); (43 (33-75) mmol/mol), p = 0.28). The prevalence of severe hypoglycemia was 3 (14%) versus 6 (12%), p = 1.00 during pregnancy and 0 versus 1, p = 1.00 during hospital admittance after delivery. Most women on degludec used one daily injection in early (20 (91%) versus 25 (49%), p = 0.001) and late pregnancy (21 (96%) versus 19 (37%), p < 0.001). No significant differences in obstetrical and neonatal outcomes were found between the groups. Maternal hospital admittance after delivery was 2 (1-5) versus 3 (2-11) days (p = 0.004). CONCLUSIONS: Glycemic control in late pregnancy, severe hypoglycemia during and immediately after pregnancy as well as pregnancy outcome were comparable in women on degludec or glargine. Degludec initiated preconceptionally may be continued in pregnancy.

Home blood pressure in pregnancy-the upper reference limit.

OBJECTIVES: To investigate whether the upper home blood pressure reference limit in healthy pregnant women correspond to 135/85 mmHg as used when diagnosing white coat hypertension outside pregnancy. METHODS: In this prospective observational study 103 healthy, singleton pregnant women with a mean age of 32 ± 4 (±SD) years and with a median pre-pregnancy body mass index of 21 (interquartile range 20-24) kg/m were included. Home blood pressure was measured with the device Microlife® BP 3A Plus twice daily for three days (18 measurements in total) in addition to routine office blood pressure measurements in early (median 12 (weeks)), mid (20) and late pregnancy (35). Upper blood pressure reference limits were calculated as mean +2 SD. RESULTS: Office blood pressure versus home blood pressure were 115 ± 11/72 ± 7 versus 103 ± 7/64 ± 5 mmHg in early pregnancy, 112 ± 11/74 ± 7 versus 102 ± 7/63 ± 5 mmHg in mid pregnancy and 118 ± 11/75 ± 8 versus 107 ± 8/66 ± 6 mmHg in late pregnancy. The mean difference between office blood pressure and home blood pressure was 10 mmHg. In late pregnancy, the upper reference limit was 140/91 mmHg for office blood pressure and 123/78 mmHg for home blood pressure with slightly lower values in early and mid pregnancy, respectively. CONCLUSION: In late pregnancy, the upper home blood pressure reference limit in a population of healthy women was 123/78 mmHg. This value questions the generally proposed level of 135/85 mmHg to define white coat hypertension in pregnancy.