Hyperglycemia and Adverse Pregnancy Outcomes

Preeclampsia is a clinical syndrome defined as the new onset of hypertension and proteinuria during the second half of pregnancy1 It afflicts 3% to 5% of pregnancies and is a leading cause of maternal mortality, especially in developing countries2,3 Because the only known remedy is delivery of the placenta, in developed countries preeclampsia is an important cause of premature delivery, usually medically indicated for the benefit of the mother This results in infant morbidity and substantial healthcare expenditure4 Despite the considerable morbidity and mortality, the cause of preeclampsia has remained enigmatic

Both hypertension and proteinuria implicate the endothelium as the target of the disease The hypertension of preeclampsia is characterized by peripheral vasoconstriction and decreased arterial compliance5,6 The proteinuria of preeclampsia is associated with a pathognomonic renal lesion known as glomerular endotheliosis, in which the endothelial cells of the glomerulus swell and endothelial fenestrations are lost7,8 Podocyturia has been recently associated with preeclampsia during clinical disease9; however, whether this is the cause or effect of proteinuria is unknown The glomerular filtration rate is decreased compared with normotensive pregnant women; in rare cases, acute renal failure may develop

Preeclampsia is a systemic vascular disorder that may also affect the liver and the brain in the mothers When the liver is involved, women may present with abdominal pain, nausea, vomiting, and elevated liver enzymes Pathological examination of the liver reveals periportal and sinusoidal fibrin deposition and, in more extreme cases, hemorrhage and necrosis10 The severe preeclampsia variant HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) occurs in ≈20% of women with severe preeclampsia,11 and is named not only for the liver involvement, but also for the disorder of the coagulation system that develops12 Approximately 20% of …

Preeclampsia, a Disease of the Maternal Endothelium The Role of Antiangiogenic Factors and Implications for Later Cardiovascular Disease

Plentiful evidence now links low birth weight due to intrauterine growth restriction and increased risk of vascular disease in later adult life This is considered to be partly the result of programming through fetal nutrition 1 In contrast, much less attention has been focused on the relation between adverse pregnancy outcomes, such as pre›eclampsia, gestational diabetes, preterm delivery, and intrauterine growth restriction, and the mother’s subsequent health, and interesting data are now increasingly linking the maternal vascular, metabolic, and inflammatory complications of pregnancy with an increased risk of vascular disease in later life (table) This article summarises the emerg› ing evidence to support this fascinating concept, notes important areas for further research, and discusses potential practical implications

https://www.bmj.com/content/bmj/325/7356/157.full.pdf

Pregnancy complications and maternal cardiovascular risk: opportunities for intervention and screening?

A Working Group on Research in Hypertension in Pregnancy was recently convened by the National Heart, Lung, and Blood Institute to determine the state of knowledge in this area and suggest appropriate directions for research. Hypertensive disorders in pregnancy, especially preeclampsia, are a leading cause of maternal death worldwide and even in developed countries increase perinatal mortality rates 5-fold. Much has been learned about preeclampsia, but gaps in the knowledge necessary to direct therapeutic strategies remain. Oxidative stress is a biologically plausible contributor to the disorder that may be amenable to intervention. Hypertension that antedates pregnancy (chronic hypertension) bears many similarities to hypertension in nonpregnant women, but the special setting of pregnancy demands information to guide evidence-based therapy. The recommendations of the Working Group are to attempt a clinical trial of antioxidant therapy to prevent preeclampsia that is be complemented by mechanistic research to increase understanding of the genetics and pathogenesis of the disorder. For chronic hypertension, clinical trials are recommended to direct choice of drugs, evaluate degree of control, and assess implications to the mother and fetus. Recommendations to increase participation in this research are also presented.

Summary of the NHLBI Working Group on Research on Hypertension During Pregnancy

Background
Mild to moderate hypertension during pregnancy is common. Antihypertensive drugs are often used in the belief that lowering blood pressure will prevent progression to more severe disease, and thereby improve the outcome.

Objectives
To assess the effects of antihypertensive drug treatments for women with mild to moderate hypertension during pregnancy.

Search methods
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013) and reference lists of retrieved studies.

Selection criteria
All randomised trials evaluating any antihypertensive drug treatment for mild to moderate hypertension during pregnancy defined, whenever possible, as systolic blood pressure 140 to 169 mmHg and diastolic blood pressure 90 to 109 mmHg. Comparisons were of one or more antihypertensive drug(s) with placebo, with no antihypertensive drug, or with another antihypertensive drug, and where treatment was planned to continue for at least seven days.

Data collection and analysis
Two review authors independently extracted data.

Main results
Forty-nine trials (4723 women) were included. Twenty-nine trials compared an antihypertensive drug with placebo/no antihypertensive drug (3350 women). There is a halving in the risk of developing severe hypertension associated with the use of antihypertensive drug(s) (20 trials, 2558 women; risk ratio (RR) 0.49; 95% confidence interval (CI) 0.40 to 0.60; risk difference (RD) -0.10 (-0.13 to -0.07); number needed to treat to harm (NNTH) 10 (8 to 13)) but little evidence of a difference in the risk of pre-eclampsia (23 trials, 2851 women; RR 0.93; 95% CI 0.80 to 1.08). Similarly, there is no clear effect on the risk of the baby dying (27 trials, 3230 women; RR 0.71; 95% CI 0.49 to 1.02), preterm birth (15 trials, 2141 women; RR 0.96; 95% CI 0.85 to 1.10), or small-for-gestational-age babies (20 trials, 2586 women; RR 0.97; 95% CI 0.80 to 1.17). There were no clear differences in any other outcomes.

Twenty-two trials (1723 women) compared one antihypertensive drug with another. Alternative drugs seem better than methyldopa for reducing the risk of severe hypertension (11 trials, 638 women; RR (random-effects) 0.54; 95% CI 0.30 to 0.95; RD -0.11 (-0.20 to -0.02); NNTH 7 (5 to 69)). There is also a reduction in the overall risk of developing proteinuria/pre-eclampsia when beta blockers and calcium channel blockers considered together are compared with methyldopa (11 trials, 997 women; RR 0.73; 95% CI 0.54 to 0.99). However, the effect on both severe hypertension and proteinuria is not seen in the individual drugs. Other outcomes were only reported by a small proportion of studies, and there were no clear differences.

Authors' conclusions
It remains unclear whether antihypertensive drug therapy for mild to moderate hypertension during pregnancy is worthwhile.

Antihypertensive drug therapy for mild to moderate hypertension during pregnancy

FIGO consensus guidelines on placenta accreta spectrum disorders: Epidemiology.

Placental abruption, classically defined as a premature separation of the placenta before delivery, is one of the leading causes of vaginal bleeding in the second half of pregnancy. Approximately 0.4-1% of pregnancies are complicated by placental abruption. The prevalence is lower in the Nordic countries (0.38-0.51%) compared with the USA (0.6-1.0%). Placental abruption is also one of the most important causes of maternal morbidity and perinatal mortality. Maternal risks include obstetric hemorrhage, need for blood transfusions, emergency hysterectomy, disseminated intravascular coagulopathy and renal failure. Maternal death is rare but seven times higher than the overall maternal mortality rate. Perinatal consequences include low birthweight, preterm delivery, asphyxia, stillbirth and perinatal death. In developed countries, approximately 10% of all preterm births and 10-20% of all perinatal deaths are caused by placental abruption. In many countries, the rate of placental abruption has been increasing. Although several risk factors are known, the etiopathogenesis of placental abruption is multifactorial and not well understood.

https://obgyn.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1600-0412.2010.01030.x

Placental abruption: epidemiology, risk factors and consequences

Insulin resistance syndrome predisposes to occlusive vascular disorders in nonpregnant subjects. Because preeclampsia, representing a pregnancy-specific occlusive vascular disorder, is known to be accompanied by metabolic changes similar to those in insulin resistance syndrome, we compared carbohydrate and lipid metabolism in 22 women who had a preeclamptic first pregnancy and in 22 control women who had normotensive first pregnancy, both, on the average, 17.0 +/- 0.7 yr earlier. The study groups were comparable in regard to body mass index at the follow-up study. Women with prior preeclampsia were normoglycemic (baseline, 3 h oral glucose tolerance), but showed a significant hyperinsulinemia, as seen from elevated immunoreactive insulin (IRI) levels at the baseline (mean +/- SE, 7.3 +/- 0.6 vs. 5.5 +/- 0.5 mU/L; P < 0.03), after 1 h (45.7 +/- 5.5 vs. 35.6 +/- 3.5 mU/L; P = 0.13), after 2 h (32.4 +/- 4.1 vs. 23.8 +/- 2.3 mU/L; P = 0.08), and after 3 h (10.1 +/- 1.4 vs. 6.4 +/- 0.6 mU/L; P = 0.02). The area under the IRI curve was larger in the women with prior preeclampsia (86.8 +/- 9.1 vs. 65.4 +/- 5.2 mU/h.L; P = 0.05). The serum levels of total cholesterol, high density lipoprotein (HDL) cholesterol (with its subfractions HDL2 and HDL3), low density lipoprotein cholesterol, triglyceride, or uric acid did not differ significantly between the study groups. In women with prior preeclamsia, the area under the IRI curve was negatively related to HDL2 cholesterol, but positively related to triglyceride and systolic blood pressure. We conclude that a history of preeclampsia is associated with mild hyperinsulinemia in nonpregnant women.

/pdf/hyperinsulinemia-17-years-after-preeclamptic-first-pregnancy-3ax7m2url7.pdf

Hyperinsulinemia 17 years after preeclamptic first pregnancy.

Objective. Placenta accreta is one of the most devastating pregnancy complications. We sought to compare outcomes between women with placenta accreta when diagnosed antenatally or intrapartum, and to define predictors of the antenatal diagnosis. Design. Retrospective case–control study. Setting. University teaching hospital. Population. Twenty-four women with placenta accreta diagnosed antenatally and 20 women discovered intrapartum. Methods. Chart review of historical and delivery-associated variables. Rates were compared between the groups. Main Outcome Measures. Placenta accreta diagnosed antenatally or intrapartum. Results. Women with antenatal diagnosis had a lower estimated blood loss of a median of 4500ml (range 100–15000ml) compared with 7800ml (range 2500–17000ml, p=0.012) and required fewer units of packed red blood cells transfused (median 7; range 0–27 compared with 13.5; range 4–31, p=0.026). Nineteen (79%) women diagnosed antenatally had balloon catheter occlusion carried out during the cesarean section. Five (21%) had the entire placenta left in situ. There was no difference in the rate of surgical complications or duration of hospitalization. The clinical diagnosis among women with antenatal diagnosis was more often placenta percreta (p=0.013). The risk factor profile of women with antenatal diagnosis of placenta accreta included higher gravidity (p=0.014) and parity (p<0.0001), history of cesarean section (p=0.004), and placenta previa in the current pregnancy (p<0.001). Conclusions. Antenatal diagnosis of placenta accreta may reduce peripartum blood loss and the need for blood transfusion. Women with antenatal diagnosis more often have placenta previa and history of previous cesarean section, and the clinical diagnosis is more often placenta percreta.

Antenatal diagnosis of placenta accreta leads to reduced blood loss

Background. To study the risk factors of placental abruption during the index pregnancy. Methods. One hundred and ninety-eight women with placental abruption and 396 control women were identified among 46,742 women who delivered at a tertiary referral university hospital between 1997 and 2001. Clinical variables were compared between the groups. Multivariate logistic regression analysis was applied to identify independent risk factors. The clinical manifestations of placental abruption were also studied. Results. The overall incidence of placental abruption was 0.42%. The independent risk factors were maternal (adjusted OR 1.8; 95% CI 1.1, 2.9) and paternal smoking (2.2; 1.3, 3.6), use of alcohol (2.2; 1.1, 4.4), placenta previa (5.7; 1.4, 23.1), pre-eclampsia (2.7; 1.3, 5.6), and chorioamnionitis (3.3; 1.0, 10.0). Vaginal bleeding (70%), abdominal pain (51%), bloody amniotic fluid (50%), and fetal heart rate abnormalities (69%) were the most common manifestations. Neither bleeding nor pain was present in 19% of the cases. Overall, 59% had preterm labor (OR 12.9; 95% CI 8.3, 19.8), and 91% were delivered by cesarean section (34.7; 20.0, 60.1). Of the newborns, 25% were growth restricted. The perinatal mortality rate was 9.2% (OR 10.1; 95% CI 3.4, 30.1). Retroplacental blood clot was seen by ultrasound in 15% of the cases. Conclusions. Maternal alcohol consumption and smoking, and smoking by the partner turned out to be independent risk factors for placental abruption. Smoking by both partners multiplied the risk. The liberal use of ultrasound examination contributed little to the management of women with placental abruption.

https://obgyn.onlinelibrary.wiley.com/doi/pdf/10.1080/00016340500449915

Minna Tikkanen

Papers

FIGO consensus guidelines on placenta accreta spectrum disorders: Epidemiology.

Placental abruption: epidemiology, risk factors and consequences

Hyperinsulinemia 17 years after preeclamptic first pregnancy.

Antenatal diagnosis of placenta accreta leads to reduced blood loss

Clinical presentation and risk factors of placental abruption.