Obesity and preeclampsia

37.1

Introduction

• Pregnant women who are obese are at risk of a multiplicity of pregnancy-related complications, in particular preeclampsia and gestational diabetes.

• It has been suggested that similar to gestational diabetes and development of type 2 diabetes, gestational hypertension and preeclampsia are revealing those with a tendency to develop cardiovascular disease.

• Obesity is known to predispose to cardiovascular disease (CVD) out with pregnancy, therefore it is important to consider that those who are obese and develop preeclampsia in pregnancy may be at a larger risk in the future.

37.2

Definitions

• Preeclampsia is defined as new onset hypertension (>140/>90 mmHg) after 20 weeks of pregnancy and the coexistence of one or more of the following new onset conditions: proteinuria (>300 mg in 24 hours or 2 ⁺ on urine dipstick), uteroplacental dysfunction and organ dysfunction such as renal insufficiency, liver involvement, neurological complications or haematological complications.

• Whereas gestational hypertension is defined as new onset hypertension after 20 weeks without proteinuria.

• Preeclampsia is described as superimposed if it occurs in a women known to have preexisting hypertension or hypertension present in the first half of pregnancy (essential or secondary hypertension with a known underlying cause).

• It is well-documented that obesity is associated with chronic hypertension. Therefore it is possible that some diagnosis of ‘preeclampsia’ in the obese is in fact unmasking of the underlying hypertension by pregnancy.

Classification of BMI as per WHO includes overweight as BMI ≥25 kg/m ² , preobese 25.00–29.99 kg/m ² , obese class I 30.00–34.99 kg/m ² , class II 35.00–39.99 kg/m ² and class III ≥40.00 kg/m ² .

37.3

Predisposition to preeclampsia

• The higher the BMI, the higher the patient’s risk of developing preeclampsia!

• One metaanalysis showed that with increasing BMI, there was an increase in risk ratio for preeclampsia with overweight being 1.70, obese 2.93 and severely obese 4.14, respectively.

• Interestingly, a study of more than half a million women showed that short stature itself was associated with an increased risk of all types of preeclampsia occurring before 32 weeks gestation.

• The UK Obstetric Surveillance System (UKOSS) study showed an incidence of preeclampsia of 9% in severely obese patients compared to 2% of nonobese controls.

  • Obesity-related metabolic abnormalities, in particular an increase in circulating insulin, raised triglycerides (TG) concentrations, and inflammation TG concentrations associated with gestational diabetes also further increase the risk of developing preeclampsia.

37.4

Pathophysiological basis of pregnancy induced hypertension (PIH) during pregnancy

• Obesity is a type of chronic inflammatory condition. During pregnancy, fat deposition is predominantly central in obese women, therefore they are at increased risk of gestational hypertension and late onset preeclampsia.

• White adipose tissue is increased in obesity and is responsible for triglyceride storage. Visceral white adipose tissue is strongly associated correlated with insulin resistance, plasma lipids, and CVD both during pregnancy as well as in the nonpregnant state.

• Physiological hyperlipidaemia is exaggerated in obese pregnant women with a greater increase in total and VLDL TG and cholesterol and small dense and low-density lipoproteins and lower high-density lipids.

• The small dense LDL particles are increased in both obesity and preeclampsia and are both atherogenic, promoting endothelial dysfunction. It is possible that dyslipidaemia in obese women triggers the development of placental bed atherosis and preeclampsia.

• It is alleged that metabolic factors including increased leptin, tumour necrosis factor-alpha (TNF-α), interleukin 1 and 8, reduced levels of adiponectin, raised insulin, glucose and lipids exacerbate the proinflammatory and antiandrogenic mechanisms of ‘placenta ischaemia-induced vascular dysfunction’, thereby increasing the risk of preeclampsia.

  • Several mechanisms have been proposed as to why obesity increases your risk of preeclampsia. Preeclampsia is suspected to be as a result of ischaemic insults in the placenta increasing antiandrogenic and proinflammatory factors; soluble fms-like tyrosine kinase-1 and TNF-α, into maternal circulation which causes maternal endothelial dysfunction.

  • It is hypothesised that as obesity is itself a chronic inflammatory condition, obese women are predisposed to an amplified inflammatory response.

37.5

The placenta

• The placenta expresses virtually all known cytokines, including TNF, resistin, and leptin, which are also produced by adipose cells and their levels are more than twofold higher in obese women.

• Adipokines also modulate placental function. Leptin regulates placental angiogenesis, protein synthesis, and growth and causes immunomodulation. Thus increased local levels of leptin may modulate placental inflammation and function,

• In obese women, a higher circulating concentration of leptin and insulin leads to impaired glucose intolerance or gestational diabetes, and possibly development of syncytiotrophoblast.

• Placentae from obese women showed a two- to threefold increase in placental macrophages as compared with nonobese women. The macrophage population was characterised by the increased expression of IL-1, TNF and IL-6. These cytokines may also increase transport of amino acids to the foetus.

• Insulin stimulates foetal aerobic glucose metabolism, reduced oxygen delivery to intervillous space, leading to thickening of the placental basement membrane and reduced uteroplacental or foetoplacental blood flow, thus causing foetal hypoxaemia. Such a change will have a compounding effect in association with cytokines-led proinflammatory changes within placental structure.