Population-based study of eclampsia: Lessons learnt to improve maternity care.

BACKGROUND: Among hypertensive disorders of pregnancy (HDP), eclampsia is a rare but serious event, often considered avoidable. Detailed assessment of the adequacy of care for the women who have eclampsia can help identify opportunities for improvement and for prevention of the associated adverse maternal and neonatal outcomes. OBJECTIVE: 1/ To estimate the incidence and describe the characteristics of women with eclampsia and to compare them with those of women with non-eclamptic hypertensive disorders of pregnancy (HDP)-related severe maternal morbidity (SMM) and of control women without SMM 2/ To analyse the quality of management in women who had eclampsia, at various stages of their care pathway. METHODS: It was a planned ancillary analysis of the EPIMOMS population-based study, conducted in six French regions in 2012-2013. Among the 182,309 maternities of the source population, all women with eclampsia (n = 51), with non-eclamptic HDP-related SMM (n = 351) and a 2% representative sample of women without SMM (n = 3,651) were included. Main outcome was the quality of care for eclampsia assessed by an independent expert panel at three different stages of management: antenatal care, care for pre-eclampsia and care for eclampsia. RESULTS: The eclampsia incidence was 2.8 per 10,000 (95%CI 2.0-4.0). Antenatal care was considered completely inadequate or substandard in 39% of women, as was pre-eclampsia care in 76%. Care for eclampsia was judged completely inadequate or substandard in 50% (21/42), mainly due to inadequate use of magnesium sulphate. CONCLUSION: The high proportion of inadequate quality of care underlines the need for an evidence-based standardisation of care for HDP.

Risk factors for placenta accreta spectrum disorders in women with any prior cesarean and a placenta previa or low lying: a prospective population-based study.

This study aimed to identify the risk factors for placenta accreta spectrum (PAS) in women who had at least one previous cesarean delivery and a placenta previa or low-lying. The PACCRETA prospective population-based study took place in 12 regional perinatal networks from 2013 through 2015. All women with one or more prior cesareans and a placenta previa or low lying were included. Placenta accreta spectrum (PAS) was diagnosed at delivery according to standardized clinical and histological criteria. Of the 520,114 deliveries, 396 fulfilled inclusion criteria; 108 were classified with PAS at delivery. Combining the number of prior cesareans and the placental location yielded a rate ranging from 5% for one prior cesarean combined with a posterior low-lying placenta to 63% for three or more prior cesareans combined with placenta previa. The factors independently associated with PAS disorders were BMI ≥ 30, previous uterine surgery, previous postpartum hemorrhage, a higher number of prior cesareans, and a placenta previa. Finally, in this high-risk population, the rate of PAS disorders varies greatly, not only with the number of prior cesareans but also with the exact placental location and some of the women's individual characteristics. Risk stratification is thus possible in this population.

The Prognosis of Glutamic Acid Decarboxylase Antibodies in Women With Hyperglycemia in Pregnancy.

CONTEXT: We recently reported that the presence of glutamic acid decarboxylase antibodies (GADA) was not associated with large-for-gestational-age infants in women with hyperglycemia in pregnancy (HIP). OBJECTIVE: We explored the association between the presence of GADA and other HIP-related adverse pregnancy outcomes. METHODS: This observational prospective study, conducted at a university hospital in a suburb of Paris, France, included 1182 consecutive women with HIP measured for GADA at HIP care initiation between 2012 and 2017. Post hoc analyses for outcomes included gestational weight gain, insulin therapy, cesarean delivery, hypertensive disorders, small-for-gestational-age infant, prematurity, and neonatal hypoglycemia. RESULTS: Of the 1182 women studied, 87 (7.4%) had positive (≥ 1 IU/mL) GADA. Although socioeconomic, clinical, and biological characteristics were similar across women in the positive and negative GADA groups, higher fasting plasma glucose values during early HIP screening were observed in the former (5.5 ± 1.5 vs 5.2 ± 0.7 mmol/L respectively, P < .001). At HIP care initiation, fructosamine levels were higher in women with positive GADA (208 ± 23 vs 200 ± 18 µmol/L; P < .05). In the homeostatic model assessment, insulin resistance (HOMA-IR) and beta secretion (HOMA-B) rates were similar in both groups. Gestational weight gain and the rates of all adverse outcomes were similar in both groups except for cesarean delivery (18.4 and 27.3% for positive and negative GADA, respectively; adjusted odds ratio 0.49 [95% CI, 0.26-0.92], P = .026). CONCLUSION: Universal measurement of GADA in women with HIP highlighted that 7.4% had positive GADA. No association was observed between GADA and HIP-related adverse pregnancy outcomes, except a lower risk of cesarean delivery.

Impact of experiencing multiple vulnerabilities on fetal growth and complications in women with hyperglycemia in pregnancy.

BACKGROUND: In women with hyperglycemia in pregnancy living in France, psychosocial deprivation is associated with both earlier and greater exposure to the condition, as well as poorer maternofetal prognosis. We explored the impact of this and two other socioeconomic vulnerability indicators-food insecurity and poor language proficiency-on adherence to prenatal care and maternal and fetal outcomes. METHODS: In a socially deprived suburb of Paris, we selected women who delivered between 01/01/2012 and 31/12/2018 and received care (nurse, dietician, diabetologist evaluation, advice, regular follow-up to adjust insulin doses if requested) for hyperglycemia in pregnancy. We analyzed the associations between individual psychosocial deprivation, food insecurity, French language proficiency (variables assessed by individual questionnaires) and fetal growth (main outcome), as well as other core maternal and fetal outcomes. RESULTS: Among the 1,168 women included (multiethnic cohort, 19.3% of whom were Europeans), 56%, 17.9%, and 27.5% had psychosocial deprivation, food insecurity, and poor French language proficiency, respectively. Forty-three percent were prescribed insulin therapy. Women with more than one vulnerability had more consultations for diabetes. The rates for small (SGA), appropriate (AGA), and large-for-gestational-age (LGA) infant were 11.4%, 76.5% and 12.2%, respectively. These rates were similar in women with and without psychosocial deprivation, and in those with and without food insecurity. Interestingly, women with poor French language proficiency had a higher odds ratio of delivering a small- or large-for-gestational age infant than those with good proficiency. CONCLUSION: We found similar pregnancy outcomes for women with hyperglycemia in pregnancy living in France, irrespective of whether or not they had psychosocial deprivation or food insecurity. Optimized single-center care with specialized follow-up could contribute to reduce inequalities in maternal and fetal outcomes in women with hyperglycemia in pregnancy.

Glycemic status during pregnancy according to fasting and post-load glucose values: The association with adverse pregnancy outcomes. An observational study.

AIM: Prognosis of treated hyperglycemia in pregnancy (HIP) may differ according to whether diagnosis following an oral glucose tolerance test (OGTT) is based on high fasting and/or high post-load glucose values. METHODS: From a multiethnic prospective study, we included 8,339 women screened for HIP after 22 weeks of gestation. We evaluated the risk of large-for-gestational-age (LGA) infant (primary endpoint) and other adverse pregnancy outcomes according to HIP status in four groups defined as follows: no HIP (n = 6,832, reference); isolated fasting HIP (n = 465), isolated post-load HIP (n = 646), and fasting and post-load HIP (n = 396). RESULTS: After adjusting for age, body mass index, ethnicity, smoking during pregnancy and parity, compared with no HIP, the adjusted odds ratios [95% confidence interval] for LGA infant were higher in the isolated fasting HIP (1.47 [1.11-1.96]) and fasting and post-load HIP (1.65 [1.23-2.21]) groups, but not in the isolated post-load HIP (1.13 [0.86-1.48]) group. The adjusted odds ratios for preterm delivery and neonatal intensive care unit were higher in the post-load HIP group (1.44 [1.03-2.03] and 1.28 [1.04-1.57], respectively), the fasting and post-load HIP group (1.81 [1.23-2.68] and 1.42 [1.10-1.81], respectively) but not in the isolated fasting HIP group (1.34 [0.90-2.00] and 1.20 [0.94-1.52], respectively). CONCLUSION: Despite glucose-lowering care and adjustment for confounders, compared with no HIP, fasting HIP was associated with a higher rate of LGA infant, whereas post-load HIP was associated with higher preterm delivery and neonatal intensive care unit admission rates.

Is there a residual risk of large-for-gestational-age infant related to gestational diabetes mellitus when it is treated?

OBJECTIVE: The hyperglycaemia and adverse pregnancy outcomes (HAPO) study, where hyperglycaemia was untreated, showed a continuous association between large-for-gestational-age (LGA) infant and seven increasing categories of fasting plasma glucose (PG), 1-hour and 2-hour PG values after a 75 g oral glucose tolerance test at 24-32 gestational weeks. We evaluated whether the excess risk persisted in the 6th and 7th glucose categories - corresponding to women treated for gestational diabetes mellitus (GDM). PATIENTS AND METHODS: We included 7,190 women meeting the HAPO criteria, of whom 655 (9.2%) were treated for GDM (dietary education in all; insulin therapy in 150 (20.3%)). We evaluated the adjusted odds ratio (aOR) for each glucose category (reference 1st category) for LGA infant. RESULTS: The aOR for LGA linearly increased from the 1st to 5th categories of fasting, 1-hour and 2-hour PG. Specifically, the aORs for the 5th category were 2.20 (95% confidence interval 1.41-3.44), 2.25 (1.11-4.59), and 2.51 (1.63-3.85), respectively. The aORs for the 6th category were globally stable at 2.52 (1.46-4.36), 2.87 (1.48-5.54), and 2.47 (1.46-4.16), respectively. The same was true for the 7th category: 1.41 (0.56-3.55), 2.84 (1.03-7.86), and 3.53 (1.77-7.06), respectively. CONCLUSION: We confirmed the association between increasing PG category and LGA infant in women without GDM. We did not observe a residual risk of LGA infant in women treated for GDM in our hospital, irrespective of elevated fasting, 1-hour, or 2-hour PG diagnosis. The risk of LGA infant was globally similar to that in women with high normal glucose values.

Metabolic characteristics and adverse pregnancy outcomes for women with hyperglycaemia in pregnancy as a function of insulin resistance.

AIM: Recent studies have shown that women with hyperglycaemia in pregnancy and insulin resistance have a greater risk of adverse pregnancy outcomes than women with normoglycaemic pregnancies. This study aimed to determine adverse pregnancy outcomes of women with hyperglycaemia in pregnancy only as a function of insulin resistance. METHODS: From a prospective cohort study, we included 1,423 women with hyperglycaemia in pregnancy whose insulin resistance was evaluated using homoeostatic model assessment for insulin resistance (HOMA-IR) when care was first provided for this condition. We compared the adverse pregnancy outcomes for different tertiles of HOMA-IR (intertertile range 1.9 and 3.3). RESULTS: Increasing HOMA-IR tertiles were positively associated with the rate of insulin therapy (tertile 1, 2 and 3: 32.7, 47.0 and 58.7%, P < 0.0001), caesarean section (23.7, 26.0 and 32.2%, respectively, P < 0.01), gestational hypertension (1.3, 2.8 and 5.4% respectively, P < 0.01), preeclampsia (1.5, 2.8 and 4.5% respectively, P < 0.05), large-for-gestational-age infant (13.3, 10.4 and 17.6% respectively, P < 0.05), and neonatal hypoglycaemia (0.8, 1.5 and 3.2% respectively, P < 0.05). Women in the 3rd HOMA-IR tertile were more likely to have insulin therapy (odds ratio 2.09 (95% interval confidence 1.61-2.71)), hypertensive disorders (2.26 (1.42-3.36)), and large-for-gestational-age infant (1.42 (1.01-1.99)) than those in the 1st and 2nd tertiles combined in multivariable logistic regression analyses adjusted for gestational age at HOMA-IR measurement, glycaemic status, age, body mass index, family history of diabetes, parity and ethnicity. CONCLUSION: Despite suitable care and increased rates of insulin therapy during pregnancy, higher insulin resistance in women with hyperglycaemia in pregnancy was associated with a greater risk of adverse pregnancy outcomes.

Edema associated with low plasma protein level and any gestational hypertension as warning signs of HELLP syndrome.

Purpose: Because preeclampsia is a multisystem disorder, its definition has recently been revised, including cases with evidence of renal, liver, neurological, or hematological dysfunction. However, the role of edema remains unclear. While the presence of mild edema is common in normal pregnancy, in severe preeclampsia protein transfer from the vascular into the interstitial compartment could lead to low serum protein level and favor the transport of fluid to the interstitial compartment.Materials and methods, Results: Over a 4-year period, 9749 women have given birth in our university maternity ward. In this period of time, 86 women developed severe preeclampsia. Among them, we retrospectively identified nine patients who first presented with mild de novo hypertension or preeclampsia, extensive edema or excessive gestational weight gain (GWG), and documented low serum protein levels; five patients also reported headache. Serum protein levels ranged from 51 to 56 g/l. We analyzed the progression of the disease in these women, and found that these patients developed criteria for complete or partial hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome in four and five cases, respectively. All patients were delivered quickly of healthy babies, and no other maternal adverse outcomes occurred.Discussion: As plasma proteins are the primary determinants of plasmatic colloid osmotic pressure (COP), headache in association with edema, low serum protein levels, and even mild hypertension, could reflect cerebral vasogenic edema with the same mechanism as for cerebral edema reported in posterior reversible encephalopathy syndrome and eclampsia. Thus, the sequential association of edema or excessive GWG with markedly low serum protein levels and mild gestational hypertension could signal the imminent development of severe preeclampsia and possibly HELLP syndrome. This sequence should be assessed in additional large-scale prospective studies.

Conservative management or cesarean hysterectomy for placenta accreta spectrum: the PACCRETA prospective study.

BACKGROUND: Placenta accreta spectrum is a life-threatening condition that has increased dramatically in recent decades along with cesarean rates worldwide. Cesarean hysterectomy is widely practiced in women with placenta accreta spectrum; however, the maternal outcomes after cesarean hysterectomy have not been thoroughly compared with the maternal outcomes after alternative approaches, such as conservative management. OBJECTIVE: This study aimed to compare the severe maternal outcomes between women with placenta accreta spectrum treated with cesarean hysterectomy and those treated with conservative management (leaving the placenta in situ). STUDY DESIGN: From a source population of 520,114 deliveries in 176 hospitals (PACCRETA study), we designed an observational cohort of women with placenta accreta spectrum who had either a cesarean hysterectomy or a conservative management (the placenta left in situ) during cesarean delivery. Clinicians prospectively identified women meeting the inclusion criteria and included them at delivery. Data collection started only after the women had received information and agreed to participate in the study in the immediate postpartum period. The primary outcome was the transfusion of >4 units of packed red blood cells within 6 months after delivery. Secondary outcomes were other maternal complications within 6 months. We used propensity score weighting to account for potential indication bias. RESULTS: Here, 86 women had conservative management and 62 women had cesarean hysterectomy for placenta accreta spectrum during cesarean delivery. The primary outcome occurred in 14 of 86 women in the conservative management group (16.3%) and 36 of 61 (59.0%) in the cesarean hysterectomy group (risk ratio in propensity score weighted model, 0.29; 95% confidence interval, 0.19-0.45). The rates of hysterectomy, total estimated blood loss exceeding 3000 mL, any blood product transfusion, adjacent organ injury, and nonpostpartum hemorrhage-related severe maternal morbidity were lower with conservative management than with cesarean hysterectomy (all adjusted, P≤.02); but, the rates of arterial embolization, endometritis, and readmission within 6 months of discharge were higher with conservative management than with cesarean hysterectomy. CONCLUSION: Among women with placenta accreta spectrum who underwent cesarean delivery, conservative management was associated with a lower risk of transfusion of >4 units of packed red blood cells within 6 months than cesarean hysterectomy.

Prognosis Associated with Sub-Types of Hyperglycaemia in Pregnancy.

We aimed to compare pregnancy outcomes in 4665 women according to the following types of hyperglycaemia in pregnancy sub-types: (i) normoglycaemia, (ii) gestational diabetes mellitus (GDM), (iii) diabetes in pregnancy (DIP), (iv) early-diagnosed (i.e., <22 weeks of gestation) GDM (eGDM), and (v) early-diagnosed DIP (eDIP). The prevalence of normoglycaemia, eGDM, eDIP, GDM, and DIP was 76.4%, 10.8%, 0.6%, 11.7%, and 0.6%, respectively. With regard to pregnancy outcomes, gestational weight gain (11.5 ± 5.5, 9.0 ± 5.4, 8.3 ± 4.7, 10.4 ± 5.3, and 10.1 ± 5.0 kg, p < 0.0001) and insulin requirement (none, 46.0%, 88.5%, 25.5%, and 51.7%; p < 0.001) differed according to the glycaemic sub-types. eGDM and eDIP were associated with higher rates of infant malformation. After adjustment for confounders, with normoglycaemia as the reference, only GDM was associated with large-for-gestational-age infant (odds ratio 1.34 (95% interval confidence 1.01-1.78) and only DIP was associated with hypertensive disorders (OR 3.48 (1.26-9.57)). To conclude, early-diagnosed hyperglycaemia was associated with an increased risk of malformation, suggesting that it was sometimes present at conception. Women with GDM, but not those with eGDM, had an increased risk of having a large-for-gestational-age infant, possibly because those with eGDM were treated early and therefore had less gestational weight gain. Women with DIP might benefit from specific surveillance for hypertensive disorders.