Background: The clinical phenotype of labor in obese women
Number previous vaginal births | Study | BMI <25.0 | BMI 25.0-29.9 | BMI 30.0-34.9 | BMI 35.0-39.9 | BMI ≥40 |
p value |
---|---|---|---|---|---|---|---|
Zero | Kominiarek et al., 2011 [19] | ||||||
Median | 5.4 hrs | 5.7 hrs | 6.0 hrs | 6.7 hrs | 7.7 hrs | <0.0001 | |
(95 % ile) | (18.2 hrs) | (18.8 hrs) | (19.9 hrs) | (22.2 hrs) | (25.6 hrs) | ||
Norman et al., 2012 [20] | |||||||
Median | 4.6 hrs | 5.0 hrs | 5.5 hrs | 6.7 hrs | <0.01 | ||
(95 % ile) | (14.4 hrs) | (15.7 hrs) | (17.3 hrs) | (21.2 hrs) | |||
One | Kominiarek et al., 2011 [19] | ||||||
Median | 4.6 hrs | 4.5 hrs | 4.7 hrs | 5.0 hrs | 5.4 hrs | <0.0001 | |
(95 % ile) | (17.5 hrs) | (17.4 hrs) | (17.9 hrs) | (19.0 hrs) | (20.6 hrs) | ||
Norman et al., 2012 [20] | |||||||
Median | 3.3 hrs | 3.9 hrs | 4.3 hrs | 5.0 hrs | <0.01 | ||
(95 % ile) | (12.6 hrs) | (15.1 hrs) | (16.5 hrs) | (19.2 hrs) |
Intrapartum intervention | Study | BMI category | Odds of use in labor, OR (95 % CI) |
---|---|---|---|
Induction of Labor | Scott-Pillai et al., 2013 [142] | Overweight | 1.2 (1.1-1.3)g, h
|
Obese | 1.3 (1.2-1.5)g, h
| ||
Obese II | 1.4 (1.3-1.6)g, h
| ||
Morbid obese | 1.6 (1.3-1.9)g, h
| ||
Garabedian et al., 2011 [143] | Overweight | 1.51 (1.42-1.60)a
| |
Obese | 2.00 (1.87-2.15) | ||
Obese II | 2.36 (2.16-2.58) | ||
Obese III | 3.66 (3.30-4.01) | ||
BMI 40–49.9 | 3.51 (3.15-3.91) | ||
BMI ≥ 50 | 5.25 (3.87-7.10) | ||
Bhattacharya et al., 2007 [9] | Overweight | 1.3 (1.2-1.4)f
| |
Obese | 1.8 (1.6-2.0)f
| ||
Morbid obese | 1.8 (1.3-2.5)f
| ||
Artificial Rupture of Membranes prior to 6 cm cervical dilation | Jensen, Agger, Rasmussen, 1999 [144] | Overweight | 1.63 (1.18-2.25)g,b
|
Obese | 1.97 (1.20-3.25)g, b
| ||
Oxytocin Augmentation of Labor | Garabedian et al., 2011 [143] | Overweight | 1.38 (1.28-1.49)a
|
Obese | 1.87 (1.70-2.06) | ||
Obese II | 2.05 (1.79-2.34) | ||
Obese III | 3.02 (2.57-3.55) | ||
BMI 40–49.9 | 3.00 (2.53-3.56) | ||
BMI ≥ 50 | 3.21 (1.97-5.23) | ||
Abenhaim & Benjamin, 2011 [145] | Overweight | 1.31 (1.15-1.49)g
| |
Obese | 1.51 (1.31-1.75)g
| ||
Morbid obese | 3.05 (1.89-4.94)g
| ||
Vahratian, 2005 [146] | Overweight | Significantly higher use in both categoriesc
| |
Obese | |||
Jensen, Agger, Rasmussen, 1999 [144] | Overweight | 1.59 (1.22-2.06)f,
b
| |
Obese | 1.98 (1.28-3.05)g,
b
| ||
Unplanned Cesarean Delivery | Vinturache et al., 2014 [147] | Overweight | |
Spontaneous labor | 1.1 (0.6-1.8) | ||
Induced labor | 1.2 (0.7-2.0) | ||
Obese | |||
Spontaneous labor | 1.5 (0.7-3.0) | ||
Induced labor | 2.2 (1.2-4.1)f
| ||
Scott-Pillai et al., 2013 [142] | Overweight | 1.4 (1.2-1.5)g, h
| |
Obese | 1.6 (1.4-1.8)g, h
| ||
Obese II | 1.8 (1.5-2.2)g, h
| ||
Morbid obese | 1.9 (1.4-2.5)g, h
| ||
Green & Shaker, 2011 [148] | BMI >35 | No sig difference once adjusted for IOLc
| |
Garabedian et al., 2011 [143] | Overweight | 1.44 (1.38-1.50)g
| |
Obese | 1.96 (1.86-2.06)g
| ||
Obese II | 2.32 (2.17-2.47)g
| ||
Obese III | 3.66 (3.39-3.95)g
| ||
BMI 40–49.9 | 3.53 (3.26-3.82)g
| ||
BMI ≥ 50 | 4.99 (4.00-6.22)g
| ||
Abenhaim & Benjamin, 2011 [145] | Overweight | 1.07 (0.80-1.43)d
| |
Obese | |||
Morbid obese | |||
Cedergren, 2009 [149] | Overweight | 1.09 (0.91-1.31) | |
Due to obstructed labor
| Obese I | 1.56 (1.14-2.14)f
| |
Obese II | 1.33 (0.72-2.46) | ||
Morbid obese | 1.79 (0.65-4.92) | ||
Cedergren, 2009 [149] | Overweight | 1.50 (1.42-1.59)g
| |
Due to ineffective uterine contractility
| Obese I | 2.14 (1.96-2.34)g
| |
Obese II | 2.72 (2.35-3.16)g
| ||
Morbid obese | 3.98 (3.14-5.04)g
| ||
Bhattacharya et al., 2007 [9] | Overweigh | 1.5 (1.3-1.6)f
| |
Obese | 2.0 (1.8-2.3)f
| ||
Morbid obese | 2.8 (2.0-3.9)f
| ||
Sukalich, Mingione, Glantz, 2006 [150] | Obese | 1.07 (1.05-1.09)f
| |
Vahratian, 2005 [146] | Overweight | 1.2 (0.8-1.8)f,
e
| |
Obese | 1.5 (1.05-2.0)f
| ||
Jensen, Agger, Rasmussen, 1999 [144] | Overweight | 1.69 (1.06-2.68)f,
b
| |
Obese | 1.91 (0.94-3.86)b
|
Overview of normal parturition physiology relevant to obesity
Preparation for parturition
Contraction & synchronization in parturition
Uterine endurance in parturition
Overview of obesity physiology relevant to pregnancy
Circulating molecules in obesity
FFA storage and meta-inflammation
Methods: a literature search for interactions between obesity and parturition signaling
Review of evidence: biologic mechanisms of labor dysfunction in obesity
Changes in labor preparation due to obesity
Placental function
Elevated leptin
Changes in labor contraction/synchronization due to obesity
Adipokines
Cholesterol
Oxytocin receptors (OTR)
Gap junctions
Changes in uterine endurance in labor due to obesity
Discussion
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Basic science investigation: We have summarized the existing evidence that obesity produces important changes in parturition signaling and the molecular program of labor in placenta, myometrium, and cervix. It is clear that each known step in the parturition process could be altered by hormones or other unique regulation produced by adipose tissue or associated meta-inflammation. However, we need to identify specific mechanisms.
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It will be important to define the type of estrogens (estriol or estradiol) produced in obese parturients and the effect of obesity on the ratio of estrogen to progesterone at term. In addition, the effect of obesity on placental hormone production and myometrial progesterone receptor expression must be quantified in both animal models and women if we are to develop new approaches to modifying the deleterious effects of obesity. -
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Preclinical animal models of obesity management in pregnancy, for example limited weight gain and intentional weight loss, may reveal important parturition and fetal effects. -
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Basic investigation of whether increased fat mass alone or associated metabolic syndrome and meta-inflammation drive parturition dysfunction is warranted. Metabolomic characterization of obese women with labor dystocia or Pitocin resistance could further our understanding of the signals linking obesity and labor outcome versus the separate influence of metabolic syndrome.
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Clinical management: Allowing additional time for obese women to complete cervical ripening and the first stage of labor before proceeding to cesarean delivery for slow labor progress could immediately improve outcomes [134, 135]. Clinical tools to identify aberrant labor progress with obesity, such as BMI-determined labor partograms, are needed. Further, investigating parturition changes with decreased weight gain or weight loss during obese pregnancy may be informative. The safety and outcome of altered prenatal and obstetric management requires thorough clinical evaluation and prospective trials [136].
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Medication management: Obese women may benefit from optimized protocols for Pitocin (and other induction/augmentation agents), rather than the universal protocols currently in use for women of any BMI. Higher doses and/or longer infusion times may be necessary for induction of labor in an obese woman. The differences in OTR expression and function and myometrial contractility between obese and normal-weight women are not yet defined. All induction agents may need to be examined to find the most effective regimen for obese cohorts.
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Therapeutic investigation:
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Cholesterol-lowering therapies (e.g., statins, niacin, bile acid sequestrants) might prevent hypercholesterolemia-linked suppression of contractions in obese women. Although statins are rated Category X in pregnancy, the teratogenic potential appears to be limited to extraordinarily high doses in animal models, and in select cases the potential benefits may outweigh the risks, even during pregnancy [137]. Randomized controlled trials (RCT) are needed. -
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Thiazolidinedione (TZD) activates peroxisome proliferator-activated receptors (PPARs), allowing for safe storage of FFA, improved insulin sensitivity, and decreased cellular ROS damage [138]. Activation of the PPAR system is known to reduce recruitment of immune cells and inhibit inflammation, allowing better utilization of glucose as an energy source for cellular processes [65]. TZD therapy could improve labor endurance by decreasing myometrial ROS damage from FFA metabolism, although the known association of TZD with increased weight gain [139] could carry other risks. A RCT of TZD therapy to improve labor endurance is needed.
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Nutrition intervention:
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Serum vitamin D is inversely related to both visceral and subcutaneous fat and insulin resistance [140], and significantly decreases biomarkers of oxidative stress [141]. A RCT investigating nutritional supplementation of anti-oxidants (e.g., vitamins D, C, E, and DHA/EPA) to modulate lipotoxicity-linked ROS elevation and improve labor outcomes is needed.