Obesity and miscarriage

Obesity is associated with an increased risk of first trimester and recurrent miscarriage. A meta-analysis of the evidence in 2006 that included 16 studies concluded that women with BMI >25 kg/m ² had significantly higher odds of miscarriage regardless of the method of conception . Using a retrospective case–control model and a sample size of 4932, Lashen et al. identified an odds ratio (OR) for spontaneous abortion of 1.2 (95% confidence interval (CI) 1.01 to 1.46) for obese women (BMI > 30 kg/m ² ). The authors also identified an increased risk of recurrent early miscarriages (more than three successive miscarriages <12 weeks’ gestation) in the obese population, OR of 3.5 (95% CI 1.03–12.01).

The exact mechanism by which obesity increases the risk of miscarriage and recurrent miscarriage is still unclear. Possible mechanisms for the association between obesity and recurrent miscarriage include an adverse impact on endometrial development or a detrimental effect on ovaries affecting oocyte quality and hence embryo viability or combination of both.

The incidence of spontaneous miscarriage has been reported to rise as insulin resistance increases . It has been suggested that insulin-sensitizing agents, such as metformin, also reduce miscarriage rates . One potential mechanism for this observation is an increased production of inflammatory and prothrombotic agents produced by adipose tissue or released from endothelium secondary to stimulation by adipocyte-derived factors. It has been suggested that plasminogen activator inhibitor-type 1 (PAI-1) is associated with increased rates of miscarriage in association with maternal obesity. Treatment with metformin appears to reduce PAI-1 and miscarriage rates .

Obesity and congenital anomaly

There is good evidence that maternal obesity confers an elevated risk of congenital anomalies, in particular neural tube defects (NTDs) and congenital heart defects (CHD). A meta-analysis of 12 observational cohort studies reporting a risk of NTD at an OR of 1.22 (95% CI 0.99–1.49), 1.70 (95% CI 1.34–2.15) and 3.11 (95% CI 1.75–5.46) for women defined as overweight, obese and severely obese, respectively, compared with healthy-weight women . An American population case–control study showed obese women had substantially increased risks of delivering offspring with anencephaly (OR 2.3, 95% CI 1.2–4.3), spina bifida (OR 2.8, 95% CI1.7–4.5) and isolated hydrocephaly (OR 2.7, 95% CI 1.5–5.0) . The risk of CHD is also significantly greater in obese women when compared to women with a normal body mass index (BMI) with ORs ranging from 1.2 to 2.0.

Obesity and ultrasound

Ultrasound assessment in obese mothers is notoriously difficult. The limitations of obstetric ultrasound as a screening test are dictated by the expertise of the clinician, the quality of the equipment and the habitus of the woman. By absorbing the associated energy, adipose tissue can significantly attenuate the ultrasound signal. Therefore, a high-frequency, higher-resolution signal would be more significantly absorbed at a lesser depth, sacrificing image quality and depth of field. A worrying consequence of maternal obesity, consequently, is the reduced sensitivity of ultrasound as a screening test for fetal anomaly.

Approximately 15% of normally visible structures will be suboptimally seen in women with a BMI above the 90th percentile . In women with a BMI above the 97.5th percentile, only 63% of structures are well visualized. The anatomic structures commonly less well seen with increasing BMI include the fetal heart, spine, kidneys, diaphragm and umbilical cord .

Obesity and gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance resulting in hyperglycaemia of variable severity with the onset or first recognition during pregnancy . GDM is estimated to affect up to 14% of pregnancies depending on the criteria used for screening and the population screened . GDM is increasing throughout the world in the wake of the increase in the incidence of obesity also among pregnant women . In a meta-analysis, Chu et al. found an unadjusted OR of 2.1 for GDM in overweight, 3.6 in obese and 8.6 in severely obese women.

In a cohort study carried out among 370,000 Danish women, who gave birth from 2004 to 2010, the risk of GDM increased with bodyweight; compared to the normal-weight women, the adjusted OR was 3.42 (3.23–3.63) for overweight women, 7.54 (7.09–8.03) for obese women and 10.83 (10.10–11.61) for severely obese women . The absolute risk for GDM was only 0.9% for normal-weight women, 3.1% for overweight women, 6.7% for obese women and 9.3% for severely obese women .

Striking data from a large prospective population-based Swedish study , which included 151,025 women, warn of the implications of inter-pregnancy weight gain. This study shows that if an increase in maternal BMI of 1–2 units occurs between pregnancies, the risk of gestational diabetes rises by 20–40%. If she becomes overweight, her risk of gestational diabetes rises by 100%. If she becomes obese, her risk of gestational diabetes rises by 200% .

Inter-pregnancy weight reduction among women with obesity has been shown to significantly reduce the risk of developing GDM. A population-based cohort study of 4102 non-diabetic women with maternal obesity prior to their first singleton pregnancy found that a weight loss of at least 4.5 kg before the second pregnancy reduced the risk of developing GDM by up to 40% .

Gestational diabetes is associated with consequences for both the mother and the child. Elevated blood glucose levels in the mother result in elevated glucose in the fetus, increasing the secretion of insulin. Insulin is a growth factor leading to macrosomia and increased risk of caesarean delivery and birth trauma (vaginal tears, shoulder dystocia and asphyxia) . Crowther et al. conducted a randomized clinical trial to determine whether treatment of women with GDM reduced the risk of perinatal complications . The rate of serious perinatal complications was significantly lower among the infants of subjects in the intervention group than among the infants of the women in the routine care group (1% vs. 4%, P = 0.01) .

Obese women with GDM are more likely to need insulin to achieve good glycemic control compared to women with normal BMIs. Langer et al. had shown in order to achieve good pregnancy outcome, the obese women with GDM will need to be treated with insulin .

Obesity and pre-eclampsia

Pre-eclampsia is defined as the occurrence of de novo hypertension (blood pressure >140/90 mmHg on two or more occasions at least 4 h apart) with proteinuria (.300 mg in 24 h or 2 + on urine dipstick) after 20 weeks’ gestation. Independent of pregnancy, hypertensive disorders are more prevalent in obese women than in their lean counterparts. Elevated pre-pregnancy BMI is an independent risk factor for the development of pre-eclampsia .

A Swedish cohort study of 805,275 pregnancies to women delivering between 1992 and 2001 found that the incidence of pre-eclampsia ranged from 1.4% among women with a BMI 19.8–26.0 to 3.5% among those with morbid obesity (BMI >40) (OR 4.82, 95% CI 4.0 4–5. 74) . Similar increases in risk have been reported for pregnancy-induced hypertension and pre-eclampsia in an Australian cohort study, in which the incidence ranged from 2.4% in women with a BMI 19.8–26.0 to 14.5% (OR 4.87, 95% CI 3.27–7.24) in women with a BMI >40 .

A systematic review of risk factors for pre-eclampsia by Duckitt et al. found that, compared to a healthy BMI, a raised booking BMI, as defined within each study, was associated with a 50% increase in the risk of pre-eclampsia, while a booking BMI >35 doubled the pre-eclampsia risk . O’Brien et al. identified 13 cohort studies, comprising nearly 1.4 million women. The risk of pre-eclampsia typically doubled with each 5–7 kg/m ² increase in pre-pregnancy BMI. This relationship persisted in studies that excluded women with chronic hypertension, diabetes mellitus and multiple gestation, or after adjustment for other confounding factors.

The mechanisms explaining the relationship between obesity and pre-eclampsia are complex and not fully understood. A number of hormonal and biochemical pathways have been implicated including insulin resistance , endothelial cell activation, dyslipidemia and elevated cytokines like the tumour necrosis factor . Different studies have shown that these hormonal and biochemical changes can be identified prior to pregnancy, in early pregnancy before the onset of pre-eclampsia and months after delivery.

Obesity and stillbirth

Maternal obesity confers an elevated risk of intrauterine demise with the risk of fetal death, particularly late and unexplained, increasing with rising BMI . A meta-analysis was conducted to summarize the epidemiological evidence on the relationship between maternal overweight and the risk of stillbirth (Chu et al., 2007). In nine studies, the unadjusted OR of a stillbirth was 1.47 (95% CI 1.08–1.94) and 2.07 (95% CI 1.59–2.74) among overweight and obese pregnant women respectively, compared with normal-weight pregnant women. The meta-analysis, however, accepted different definitions for BMI categories and only five studies were known to use the same definition of stillbirth . No single cause is particularly identified for this elevated risk; however, both unexplained intrauterine demise and placental dysfunction appear to predominate .

Obesity and macrosomia

Maternal weight and maternal weight gain during pregnancy exert an important influence on the birthweight of the infant . Increased maternal BMI confers an elevated risk of delivering a heavier infant , while increasing maternal weight gain during pregnancy is independently related to increasing birthweight of the infant . Maternal weight gain of more than 11 kg is strongly associated with the birth of a large-for-gestational-age neonate .

Sheiner et al. analyzed pregnancy outcomes in a cohort of 126,080 deliveries. Patients with hypertension and diabetes were excluded. Obese women (BMI > 30 kg/m ² ) had an increased risk of fetal macrosomia with an OR of 1.4 (95% CI 1.2– 1.7). The use of antenatal ultrasound to detect fetal macrosomia is associated with increased obstetric interventions such as induction of labour and caesarean section . Although fetal macrosomia is a risk factor for shoulder dystocia, the absolute risk of a severe shoulder dystocia associated with permanent impairment, or death, remains low . When the sensitivity and specificity of ultrasound to predict a birthweight >4500 g are included, it is estimated that 3695 non-diabetic women would require caesarean section to prevent a single case of permanent brachial plexus injury due to shoulder dystocia .

Obesity and prolonged pregnancy

Prolonged pregnancy is defined as a pregnancy that lasts for more than 294 days compared with term gestation that is between 260 and 293 days. A recent Swedish Retrospective Study of 186,087 primiparous women concluded that a higher maternal BMI in the first trimester was associated with longer gestation and an increased risk of post-date pregnancy . In another retrospective cohort study of 29,224 women with singleton pregnancies, it was found that higher maternal BMI at booking is associated with an increased risk of prolonged labour and an increased rate of induction of labour .

The mechanisms for the association between prolonged pregnancy and obesity remain unclear. Circulating levels of corticotrophin-releasing hormone (CRH), mainly synthesized by the placenta and cortisol may play a role in the onset on labour. There is an inverse linear correlation between plasma cortisol and relative weight, thereby contributing to prolonged pregnancy . Another potential mechanism which is that the metabolism of oestrogen by the adipose tissue of obese women may result in an alteration in the oestrogen–progesterone ratio in maternal plasma which in turn has a role in the initiation of labour .

Obesity and intrapartum monitoring

Monitoring contractions and assessing adequate labour progress can be challenging in obese women . Manual palpation and/or external toco-dynamometry are most commonly used, but in obese women, the distance between the skin and the uterus would render this technique inaccurate. In one study of 50 women with a BMI >35 kg/m ² , difficulties in monitoring contractions was encountered in 30% of obese women. Newer techniques, such as electrohysterography, may prove superior to both toco-dynamometry and intrauterine pressure assessment for labour monitoring in this population .

External fetal monitoring is at times more difficult in the presence of maternal obesity given the challenge of transducing the fetal heart through the maternal pannus. While there is no specific requirement for continuous electronic fetal monitoring in labour in an otherwise uncomplicated pregnancy, many obese women will have other indications for continuous fetal monitoring, such as hypertension, gestational diabetes or induction of labour .

Obesity and caesarean section

The risk of caesarean section is increased in the obese parturient. Dietz et al. analyzed 24,423 nulliparous women stratified by pre-pregnancy BMI and pregnancy complications. The caesarean section rate was 14.3% for lean women (BMI < 19.8 kg/m ² ) and 42.6% for very obese women (BMI 35 kg/m ² ). In a 2007 meta-analysis of 33 studies, the unadjusted ORs of a caesarean delivery were 1.46 (CI 1.34–1.60), 2.05 (CI 1.86–2.27) and 2.89 (CI 2.28–3.79) among overweight, obese and severely obese women, respectively, compared with normal-weight women . The increase was also independent of gestational diabetes mellitus. A 2008 meta-analysis found that the CS rate was twice as high in the obese BMI category compared with the ideal BMI . However, the increase was significant for emergency sections ( n = 6 studies), but not for elective sections ( n = 3 studies).

The increase in the rate of caesarean section may be due, in part, to the fact that overweight and obese nulliparous women progress more slowly through the first stage of labour . When faced with lack of descent in the second stage of labour, some practitioners may opt for caesarean section rather than operative vaginal delivery because of concerns about fetal macrosomia and shoulder dystocia .

Caesarean section is associated with an increased morbidity in obese women . In the case of an emergency caesarean section, delays from decision to delivery may occur due to longer time for patient transport and set-up, establishment of anaesthesia and longer operative time, including incision-to-delivery time . Thomas et al. reviewed 17,780 emergency caesarean sections performed in 2000 in England and Wales. Only 22% of women were delivered within 30 min. Of the 4622 caesarean sections performed for immediate threat to the life of the mother or fetus, only 46% were achieved within 30 min.

In morbidly obese women, blood loss during caesarean section is expectedly greater than in normal-weight women. In this group of women, blood loss more than 1000 ml was 34.9% versus 9.3% in non-obese women . The incidence of post-partum haemorrhage varies from no increase to a 70% increase in morbidly obese women . Blood loss is always difficult to quantify and a more useful outcome could be the number of packed red cell transfusions given. A higher BMI is nevertheless strongly correlated with post-partum anaemia, the risk being 2.8 times higher (95% CI 1.7–4.7) .

Rates of post-operative infection are higher in obese women . The increase in infectious morbidity is also seen in elective cases, even when perioperative antibiotics are administered. A retrospective review of 287,213 deliveries reported an adjusted OR of 2.24 (95% CI 1.91–2.64) for wound infection in obese women compared with healthy-weight women . In women with a BMI over 40 kg/m ² , wound infection occurs more frequently with an adjusted OR of 3.95 (95% CI 1.77–8.82) . In women with a BMI >50 kg/m ² , wound infection occurred in 66% and wound dehiscence in 14% of cases . Admission to the intensive care unit occurs more commonly among women with a BMI >50 kg/m ² compared with women of normal weight (adjusted odds ratio (AOR) 3.86; 95% CI 1.41–10.6) . Obesity and its complications are also associated with longer hospital stays and higher costs .

In the absence of contraindications, women who have had their first child by caesarean section are asked to consider vaginal birth in subsequent pregnancies . Obese women are less likely than their lean peers to be successful in delivering vaginally after a previous caesarean section. In women with a BMI >29 kg/m ² , the success rate is 54–68% . The rate of success is further reduced in even heavier women. Chauhan et al. found a 13% vaginal birth after caesarean (VBAC) success rate in women >300 lbs (136 kg). Women with obesity have additional risks needing consideration and morbid obesity carries a greater risk for uterine rupture during trial of labour and neonatal injury.

Obesity and obstetrics anaesthetics

Obese women are more likely to require general anaesthesia for caesarean delivery, with an increased risk of difficult or failed intubation and gastric aspiration . A 6-year review of failed intubations in obstetric patients in a United Kingdom region reported 36 cases of failed intubation; the average BMI of these women was found to be 33 .

In obese patients, the risk of epidural failure is increased. Inability to identify landmarks, difficulty in placing the regional block and erratic spread of the anaesthetic solution contribute to the failure rate . The initial failure rate for epidural catheter placement can be very high (42%) , and multiple attempts at catheter placement may be required. More than a single attempt is necessary for successful epidural placement in approximately 75% of morbidly obese women. and more than three attempts are needed in 14% .