Julianna Schantz-Dunn, MD, MPH

Cesarean birth is one of the most common major surgical procedures performed in developed countries¹ with over 1,170,000 cesarean births in the United States in 2021.² Many surgeons and anesthesiologists believe that Enhanced Recovery after Surgery (ERAS) pathways improve surgical outcomes.^3,4 Important goals of ERAS include setting patient expectations for the surgical procedure, accelerating patient recovery to full function, and minimizing perioperative complications such as severe nausea, aspiration, surgical site infection, wound complications, and perioperative anemia. The ERAS Society in 2018^5-7 and the Society for Obstetric Anesthesia and Perinatology (SOAP) in 2021⁸ proposed ERAS pathways for cesarean birth. Both societies recommended that obstetric units consider adopting an ERAS pathway compatible with local clinical resources. In addition, the American College of Obstetricians and Gynecologists (ACOG) has provided guidance for implementing ERAS pathways for gynecologic surgery.⁹ The consistent use of standardized protocols to improve surgical care in obstetrics should lead to a reduction in care variation and improve health equity outcomes.

The clinical interventions recommended for ERAS cesarean birth occur sequentially in the preoperative, intraoperative, and postoperative phases of care. The recommendations associated with each of these phases are reviewed below. It is important to note that each obstetric unit should use a multidisciplinary process to develop an ERAS pathway that best supports local practice given clinician preferences, patient characteristics, and resource availability.
 

Preoperative components of ERAS

Standardized patient education (SPE). SPE is an important component of ERAS, although evidence to support the recommendation is limited. At a minimum a written handout describing steps in the cesarean birth process, or a patient-education video should be part of patient education. The University of Michigan Medical Center has produced a 3-minute video for patients explaining ERAS cesarean birth.¹⁰ The University of Maryland Medical Center has produced a 2.5-minute video in English and Spanish, explaining ERAS cesarean birth for patients.¹¹ Some surgeons place a telephone call to patients the evening before surgery to help orient the patient to ERAS cesarean birth.

Breastfeeding education. An important goal of obstetric care is to optimize the rate of exclusive breastfeeding at birth. Breastfeeding education, including a commitment to support the initiation of breastfeeding within 1 hour of birth, may enhance the rate of exclusive breastfeeding. There are numerous videos available for patients about breastfeeding after cesarean birth (as an example, see: https://www.youtube.com/watch?v=9iOGn85NdTg).

Limit fasting. In the past, surgical guidelines recommended fasting after midnight prior to surgery. The ERAS Society recommends that patients should be encouraged to drink clear fluids up to 2 hours before surgery and may have a light meal up to 6 hours before surgery (Part 1).

Carbohydrate loading. Surgery causes a metabolic stress that is increased by fasting. Carbohydrate loading prior to surgery reduces the magnitude of the catabolic state caused by the combination of surgery and fasting.¹² SOAP and the ERAS Society recommend oral carbohydrate fluid supplementation 2 hours before surgery for nondiabetic patients. SOAP suggests 32 oz of Gatorade or 16 oz of clear apple juice as options for carbohydrate loading. For diabetic patients, the carbohydrate load can be omitted. In fasting pregnant patients at term, gastric emptying was near complete 2 hours after consumption of 400 mL of a carbohydrate drink.¹³ In one study, consumption of 400 mL of a carbohydrate drink 2 hours before cesarean resulted in a 7% increase in the newborn blood glucose level at 20 min after delivery.¹⁴

Minimize preoperative anemia. Approximately 50% of pregnant women are iron deficient and approximately 10% are anemic in the third trimester.^15,16 Cesarean birth is associated with significant blood loss necessitating the need to optimize red blood cell mass before surgery. Measuring ferritin to identify patients with iron deficiency and aggressive iron replacement, including intravenous iron if necessary, will reduce the prevalence of anemia prior to cesarean birth.¹⁷ Another cause of anemia in pregnancy is vitamin B12 (cobalamin) deficiency. Low vitamin B12 is especially common in pregnant patients who have previously had bariatric surgery. One study reported that, of 113 pregnant patients who were, on average, 3 years from a bariatric surgery procedure, 12% had vitamin B12 circulating levels < 130 pg/mL.¹⁸ Among pregnant patients who are anemic, and do not have a hemoglobinopathy, measuring ferritin, folic acid, and vitamin B12 will help identify the cause of anemia and guide treatment.¹⁹

Optimize preoperative physical condition. Improving healthy behaviors and reducing unhealthy behaviors preoperatively may enhance patient recovery to full function. In the weeks before scheduled cesarean birth, cessation of the use of tobacco products, optimizing activity and improving diet quality, including increasing protein intake, may best prepare patients for the metabolic stress of surgery.

Continue to: Intraoperative components of ERAS...

Intraoperative components of ERAS

Reduce the risk of surgical site infection (SSI) and wound complications. Bundles that include antibiotics, chlorhexidine (or an alternative antibacterial soap) and clippers have been shown to reduce SSI.²⁰ Routine administration of preoperative antibiotics is a consensus recommendation and there is high adherence with this recommendation in the United States. Chlorhexidine-alcohol is the preferred solution for skin preparation. Vaginal preparation with povidine-iodine or chlorhexidine may be considered.⁶

Surgical technique. Blunt extension of a transverse hysterotomy may reduce blood loss. Closure of the hysterotomy incision in 2 layers is recommended to reduce uterine scar dehiscence in a subsequent pregnancy. If the patient has ≥2 cm of subcutaneous tissue, this layer should be approximated with sutures. Skin closure should be with subcuticular suture.⁶

Optimize uterotonic administration. Routine use of uterotonics reduces the risk of blood loss, transfusion, and postoperative anemia. There is high adherence with the use of uterotonic administration after birth in the United States.^6,8

Ensure normothermia. Many patients become hypothermic during a cesarean birth. Active warming of the patient with an in-line IV fluid warmer and forced air warming over the patient’s body can reduce the risk of hypothermia.⁸

Initiate multimodal anesthesia. Anesthesiologists often use intrathecal or epidural morphine to enhance analgesia. Ketorolac administration prior to completion of the cesarean procedure and perioperative administration of acetaminophen may reduce postoperative pain.⁸ The use of preoperative antiemetics will reduce intraoperative and postoperative nausea and vomiting.

Initiate VTE prophylaxis. Pneumatic compression stockings are recommended. Anticoagulation should not be routinely used for VTE prophylaxis.⁶

Postoperative components of ERAS

Patient education to prepare for discharge home when ready. Patient education focused on home when ready is important in preparing the patient for discharge home.⁷ Completion of required newborn testing, lactation education, and contraception planning plus coordination of newborn pediatric follow-up is necessary before discharge.

Support early return of bowel function. Early return of bowel function is best supported by a multimodal approach including initiation of clear fluid intake immediately following surgery, encouraging consumption of a regular diet within 2⁷ to 4 hours⁸ following surgery. Gum chewing for at least 5 minutes 3 times daily accelerates return of bowel function.⁸ In a meta-analysis of 10 randomized studies examining the effect of gum chewing after cesarean, the investigators reported that gum chewing shortened the time to passage of flatus and defecation.²¹

Early ambulation.

Sequentially advanced activity, starting with sitting on the edge of the bed, sitting in a chair, and ambulation within 8 hours of surgery, is recommended to facilitate faster recovery, reduce rates of complications, and enable transition to home.⁸

Early removal of the urinary catheter. It is recommended that the urinary catheter be removed within 12 hours after cesarean birth.⁸ Early removal of the urinary catheter increases patient mobility and reduces the length of hospitalization. Early removal of the urinary catheter may be associated with postoperative urinary retention and recatheterization in a small number of patients.

Prescribe routinely scheduled acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs) and ketorolac. A key component of ERAS cesarean birth is the standardized administration of nonopioid pain medicines, alternating doses of acetaminophen and an NSAID. ERAS cesarean birth is likely to result in a reduction in inpatient and postdischarge opioid use.^22-24

VTE prophylaxis. Pneumatic compression stockings are recommended. Anticoagulation should not be routinely used for VTE prophylaxis.⁸

Auditing and reporting adherence with components of ERAS

In clinical practice there may be a gap between a clinician’s subjective perception of their performance and an independent audit of their clinical performance. ERAS pathways should be implemented with a commitment to performing audits and providing quantitative feedback to clinicians. Consistent use of measurement, feedback, and coaching can improve performance and reduce variation among individual clinicians. As an example, in one study of the use of a surgical safety checklist, 99% of the surgeons reported that they routinely used a surgical safety checklist, but the audit showed that the checklist was used in only 60% of cases.²⁵ Gaps between self-reported performance and audited performance are common in clinical practice. Audits with feedback are critical to improving adherence with the components of an ERAS pathway.

Three independent systematic reviews and meta-analyses report that ERAS pathways reduce hospital length of stay without increasing the readmission rate.^26-28 One meta-analysis reported that ERAS may also reduce time to first mobilization and result in earlier removal of the urinary catheter.²⁶ ERAS pathways also may reduce postoperative complications, lower pain scores, and decrease opioid use.²⁷ The general consensus among quality and safety experts is that reducing variation through standardization of pathways is generally associated with improved quality and enhanced safety. ERAS pathways have been widely accepted in multiple surgical fields. ERAS pathways should become the standard for performing cesarean procedures.●

Cesarean birth is one of the most common major surgical procedures performed in developed countries¹ with over 1,170,000 cesarean births in the United States in 2021.² Many surgeons and anesthesiologists believe that Enhanced Recovery after Surgery (ERAS) pathways improve surgical outcomes.^3,4 Important goals of ERAS include setting patient expectations for the surgical procedure, accelerating patient recovery to full function, and minimizing perioperative complications such as severe nausea, aspiration, surgical site infection, wound complications, and perioperative anemia. The ERAS Society in 2018^5-7 and the Society for Obstetric Anesthesia and Perinatology (SOAP) in 2021⁸ proposed ERAS pathways for cesarean birth. Both societies recommended that obstetric units consider adopting an ERAS pathway compatible with local clinical resources. In addition, the American College of Obstetricians and Gynecologists (ACOG) has provided guidance for implementing ERAS pathways for gynecologic surgery.⁹ The consistent use of standardized protocols to improve surgical care in obstetrics should lead to a reduction in care variation and improve health equity outcomes.

The clinical interventions recommended for ERAS cesarean birth occur sequentially in the preoperative, intraoperative, and postoperative phases of care. The recommendations associated with each of these phases are reviewed below. It is important to note that each obstetric unit should use a multidisciplinary process to develop an ERAS pathway that best supports local practice given clinician preferences, patient characteristics, and resource availability.
 

Preoperative components of ERAS

Standardized patient education (SPE). SPE is an important component of ERAS, although evidence to support the recommendation is limited. At a minimum a written handout describing steps in the cesarean birth process, or a patient-education video should be part of patient education. The University of Michigan Medical Center has produced a 3-minute video for patients explaining ERAS cesarean birth.¹⁰ The University of Maryland Medical Center has produced a 2.5-minute video in English and Spanish, explaining ERAS cesarean birth for patients.¹¹ Some surgeons place a telephone call to patients the evening before surgery to help orient the patient to ERAS cesarean birth.

Breastfeeding education. An important goal of obstetric care is to optimize the rate of exclusive breastfeeding at birth. Breastfeeding education, including a commitment to support the initiation of breastfeeding within 1 hour of birth, may enhance the rate of exclusive breastfeeding. There are numerous videos available for patients about breastfeeding after cesarean birth (as an example, see: https://www.youtube.com/watch?v=9iOGn85NdTg).

Limit fasting. In the past, surgical guidelines recommended fasting after midnight prior to surgery. The ERAS Society recommends that patients should be encouraged to drink clear fluids up to 2 hours before surgery and may have a light meal up to 6 hours before surgery (Part 1).

Carbohydrate loading. Surgery causes a metabolic stress that is increased by fasting. Carbohydrate loading prior to surgery reduces the magnitude of the catabolic state caused by the combination of surgery and fasting.¹² SOAP and the ERAS Society recommend oral carbohydrate fluid supplementation 2 hours before surgery for nondiabetic patients. SOAP suggests 32 oz of Gatorade or 16 oz of clear apple juice as options for carbohydrate loading. For diabetic patients, the carbohydrate load can be omitted. In fasting pregnant patients at term, gastric emptying was near complete 2 hours after consumption of 400 mL of a carbohydrate drink.¹³ In one study, consumption of 400 mL of a carbohydrate drink 2 hours before cesarean resulted in a 7% increase in the newborn blood glucose level at 20 min after delivery.¹⁴

Minimize preoperative anemia. Approximately 50% of pregnant women are iron deficient and approximately 10% are anemic in the third trimester.^15,16 Cesarean birth is associated with significant blood loss necessitating the need to optimize red blood cell mass before surgery. Measuring ferritin to identify patients with iron deficiency and aggressive iron replacement, including intravenous iron if necessary, will reduce the prevalence of anemia prior to cesarean birth.¹⁷ Another cause of anemia in pregnancy is vitamin B12 (cobalamin) deficiency. Low vitamin B12 is especially common in pregnant patients who have previously had bariatric surgery. One study reported that, of 113 pregnant patients who were, on average, 3 years from a bariatric surgery procedure, 12% had vitamin B12 circulating levels < 130 pg/mL.¹⁸ Among pregnant patients who are anemic, and do not have a hemoglobinopathy, measuring ferritin, folic acid, and vitamin B12 will help identify the cause of anemia and guide treatment.¹⁹

Optimize preoperative physical condition. Improving healthy behaviors and reducing unhealthy behaviors preoperatively may enhance patient recovery to full function. In the weeks before scheduled cesarean birth, cessation of the use of tobacco products, optimizing activity and improving diet quality, including increasing protein intake, may best prepare patients for the metabolic stress of surgery.

Continue to: Intraoperative components of ERAS...

Intraoperative components of ERAS

Reduce the risk of surgical site infection (SSI) and wound complications. Bundles that include antibiotics, chlorhexidine (or an alternative antibacterial soap) and clippers have been shown to reduce SSI.²⁰ Routine administration of preoperative antibiotics is a consensus recommendation and there is high adherence with this recommendation in the United States. Chlorhexidine-alcohol is the preferred solution for skin preparation. Vaginal preparation with povidine-iodine or chlorhexidine may be considered.⁶

Surgical technique. Blunt extension of a transverse hysterotomy may reduce blood loss. Closure of the hysterotomy incision in 2 layers is recommended to reduce uterine scar dehiscence in a subsequent pregnancy. If the patient has ≥2 cm of subcutaneous tissue, this layer should be approximated with sutures. Skin closure should be with subcuticular suture.⁶

Optimize uterotonic administration. Routine use of uterotonics reduces the risk of blood loss, transfusion, and postoperative anemia. There is high adherence with the use of uterotonic administration after birth in the United States.^6,8

Ensure normothermia. Many patients become hypothermic during a cesarean birth. Active warming of the patient with an in-line IV fluid warmer and forced air warming over the patient’s body can reduce the risk of hypothermia.⁸

Initiate multimodal anesthesia. Anesthesiologists often use intrathecal or epidural morphine to enhance analgesia. Ketorolac administration prior to completion of the cesarean procedure and perioperative administration of acetaminophen may reduce postoperative pain.⁸ The use of preoperative antiemetics will reduce intraoperative and postoperative nausea and vomiting.

Initiate VTE prophylaxis. Pneumatic compression stockings are recommended. Anticoagulation should not be routinely used for VTE prophylaxis.⁶

Postoperative components of ERAS

Patient education to prepare for discharge home when ready. Patient education focused on home when ready is important in preparing the patient for discharge home.⁷ Completion of required newborn testing, lactation education, and contraception planning plus coordination of newborn pediatric follow-up is necessary before discharge.

Support early return of bowel function. Early return of bowel function is best supported by a multimodal approach including initiation of clear fluid intake immediately following surgery, encouraging consumption of a regular diet within 2⁷ to 4 hours⁸ following surgery. Gum chewing for at least 5 minutes 3 times daily accelerates return of bowel function.⁸ In a meta-analysis of 10 randomized studies examining the effect of gum chewing after cesarean, the investigators reported that gum chewing shortened the time to passage of flatus and defecation.²¹

Early ambulation.

Sequentially advanced activity, starting with sitting on the edge of the bed, sitting in a chair, and ambulation within 8 hours of surgery, is recommended to facilitate faster recovery, reduce rates of complications, and enable transition to home.⁸

Early removal of the urinary catheter. It is recommended that the urinary catheter be removed within 12 hours after cesarean birth.⁸ Early removal of the urinary catheter increases patient mobility and reduces the length of hospitalization. Early removal of the urinary catheter may be associated with postoperative urinary retention and recatheterization in a small number of patients.

Prescribe routinely scheduled acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs) and ketorolac. A key component of ERAS cesarean birth is the standardized administration of nonopioid pain medicines, alternating doses of acetaminophen and an NSAID. ERAS cesarean birth is likely to result in a reduction in inpatient and postdischarge opioid use.^22-24

VTE prophylaxis. Pneumatic compression stockings are recommended. Anticoagulation should not be routinely used for VTE prophylaxis.⁸

Auditing and reporting adherence with components of ERAS

In clinical practice there may be a gap between a clinician’s subjective perception of their performance and an independent audit of their clinical performance. ERAS pathways should be implemented with a commitment to performing audits and providing quantitative feedback to clinicians. Consistent use of measurement, feedback, and coaching can improve performance and reduce variation among individual clinicians. As an example, in one study of the use of a surgical safety checklist, 99% of the surgeons reported that they routinely used a surgical safety checklist, but the audit showed that the checklist was used in only 60% of cases.²⁵ Gaps between self-reported performance and audited performance are common in clinical practice. Audits with feedback are critical to improving adherence with the components of an ERAS pathway.

Three independent systematic reviews and meta-analyses report that ERAS pathways reduce hospital length of stay without increasing the readmission rate.^26-28 One meta-analysis reported that ERAS may also reduce time to first mobilization and result in earlier removal of the urinary catheter.²⁶ ERAS pathways also may reduce postoperative complications, lower pain scores, and decrease opioid use.²⁷ The general consensus among quality and safety experts is that reducing variation through standardization of pathways is generally associated with improved quality and enhanced safety. ERAS pathways have been widely accepted in multiple surgical fields. ERAS pathways should become the standard for performing cesarean procedures.●

Cesarean birth is one of the most common major surgical procedures performed in developed countries¹ with over 1,170,000 cesarean births in the United States in 2021.² Many surgeons and anesthesiologists believe that Enhanced Recovery after Surgery (ERAS) pathways improve surgical outcomes.^3,4 Important goals of ERAS include setting patient expectations for the surgical procedure, accelerating patient recovery to full function, and minimizing perioperative complications such as severe nausea, aspiration, surgical site infection, wound complications, and perioperative anemia. The ERAS Society in 2018^5-7 and the Society for Obstetric Anesthesia and Perinatology (SOAP) in 2021⁸ proposed ERAS pathways for cesarean birth. Both societies recommended that obstetric units consider adopting an ERAS pathway compatible with local clinical resources. In addition, the American College of Obstetricians and Gynecologists (ACOG) has provided guidance for implementing ERAS pathways for gynecologic surgery.⁹ The consistent use of standardized protocols to improve surgical care in obstetrics should lead to a reduction in care variation and improve health equity outcomes.

The clinical interventions recommended for ERAS cesarean birth occur sequentially in the preoperative, intraoperative, and postoperative phases of care. The recommendations associated with each of these phases are reviewed below. It is important to note that each obstetric unit should use a multidisciplinary process to develop an ERAS pathway that best supports local practice given clinician preferences, patient characteristics, and resource availability.
 

Preoperative components of ERAS

Standardized patient education (SPE). SPE is an important component of ERAS, although evidence to support the recommendation is limited. At a minimum a written handout describing steps in the cesarean birth process, or a patient-education video should be part of patient education. The University of Michigan Medical Center has produced a 3-minute video for patients explaining ERAS cesarean birth.¹⁰ The University of Maryland Medical Center has produced a 2.5-minute video in English and Spanish, explaining ERAS cesarean birth for patients.¹¹ Some surgeons place a telephone call to patients the evening before surgery to help orient the patient to ERAS cesarean birth.

Breastfeeding education. An important goal of obstetric care is to optimize the rate of exclusive breastfeeding at birth. Breastfeeding education, including a commitment to support the initiation of breastfeeding within 1 hour of birth, may enhance the rate of exclusive breastfeeding. There are numerous videos available for patients about breastfeeding after cesarean birth (as an example, see: https://www.youtube.com/watch?v=9iOGn85NdTg).

Limit fasting. In the past, surgical guidelines recommended fasting after midnight prior to surgery. The ERAS Society recommends that patients should be encouraged to drink clear fluids up to 2 hours before surgery and may have a light meal up to 6 hours before surgery (Part 1).

Carbohydrate loading. Surgery causes a metabolic stress that is increased by fasting. Carbohydrate loading prior to surgery reduces the magnitude of the catabolic state caused by the combination of surgery and fasting.¹² SOAP and the ERAS Society recommend oral carbohydrate fluid supplementation 2 hours before surgery for nondiabetic patients. SOAP suggests 32 oz of Gatorade or 16 oz of clear apple juice as options for carbohydrate loading. For diabetic patients, the carbohydrate load can be omitted. In fasting pregnant patients at term, gastric emptying was near complete 2 hours after consumption of 400 mL of a carbohydrate drink.¹³ In one study, consumption of 400 mL of a carbohydrate drink 2 hours before cesarean resulted in a 7% increase in the newborn blood glucose level at 20 min after delivery.¹⁴

Minimize preoperative anemia. Approximately 50% of pregnant women are iron deficient and approximately 10% are anemic in the third trimester.^15,16 Cesarean birth is associated with significant blood loss necessitating the need to optimize red blood cell mass before surgery. Measuring ferritin to identify patients with iron deficiency and aggressive iron replacement, including intravenous iron if necessary, will reduce the prevalence of anemia prior to cesarean birth.¹⁷ Another cause of anemia in pregnancy is vitamin B12 (cobalamin) deficiency. Low vitamin B12 is especially common in pregnant patients who have previously had bariatric surgery. One study reported that, of 113 pregnant patients who were, on average, 3 years from a bariatric surgery procedure, 12% had vitamin B12 circulating levels < 130 pg/mL.¹⁸ Among pregnant patients who are anemic, and do not have a hemoglobinopathy, measuring ferritin, folic acid, and vitamin B12 will help identify the cause of anemia and guide treatment.¹⁹

Optimize preoperative physical condition. Improving healthy behaviors and reducing unhealthy behaviors preoperatively may enhance patient recovery to full function. In the weeks before scheduled cesarean birth, cessation of the use of tobacco products, optimizing activity and improving diet quality, including increasing protein intake, may best prepare patients for the metabolic stress of surgery.

Continue to: Intraoperative components of ERAS...

Intraoperative components of ERAS

Reduce the risk of surgical site infection (SSI) and wound complications. Bundles that include antibiotics, chlorhexidine (or an alternative antibacterial soap) and clippers have been shown to reduce SSI.²⁰ Routine administration of preoperative antibiotics is a consensus recommendation and there is high adherence with this recommendation in the United States. Chlorhexidine-alcohol is the preferred solution for skin preparation. Vaginal preparation with povidine-iodine or chlorhexidine may be considered.⁶

Surgical technique. Blunt extension of a transverse hysterotomy may reduce blood loss. Closure of the hysterotomy incision in 2 layers is recommended to reduce uterine scar dehiscence in a subsequent pregnancy. If the patient has ≥2 cm of subcutaneous tissue, this layer should be approximated with sutures. Skin closure should be with subcuticular suture.⁶

Optimize uterotonic administration. Routine use of uterotonics reduces the risk of blood loss, transfusion, and postoperative anemia. There is high adherence with the use of uterotonic administration after birth in the United States.^6,8

Ensure normothermia. Many patients become hypothermic during a cesarean birth. Active warming of the patient with an in-line IV fluid warmer and forced air warming over the patient’s body can reduce the risk of hypothermia.⁸

Initiate multimodal anesthesia. Anesthesiologists often use intrathecal or epidural morphine to enhance analgesia. Ketorolac administration prior to completion of the cesarean procedure and perioperative administration of acetaminophen may reduce postoperative pain.⁸ The use of preoperative antiemetics will reduce intraoperative and postoperative nausea and vomiting.

Initiate VTE prophylaxis. Pneumatic compression stockings are recommended. Anticoagulation should not be routinely used for VTE prophylaxis.⁶

Postoperative components of ERAS

Patient education to prepare for discharge home when ready. Patient education focused on home when ready is important in preparing the patient for discharge home.⁷ Completion of required newborn testing, lactation education, and contraception planning plus coordination of newborn pediatric follow-up is necessary before discharge.

Support early return of bowel function. Early return of bowel function is best supported by a multimodal approach including initiation of clear fluid intake immediately following surgery, encouraging consumption of a regular diet within 2⁷ to 4 hours⁸ following surgery. Gum chewing for at least 5 minutes 3 times daily accelerates return of bowel function.⁸ In a meta-analysis of 10 randomized studies examining the effect of gum chewing after cesarean, the investigators reported that gum chewing shortened the time to passage of flatus and defecation.²¹

Early ambulation.

Sequentially advanced activity, starting with sitting on the edge of the bed, sitting in a chair, and ambulation within 8 hours of surgery, is recommended to facilitate faster recovery, reduce rates of complications, and enable transition to home.⁸

Early removal of the urinary catheter. It is recommended that the urinary catheter be removed within 12 hours after cesarean birth.⁸ Early removal of the urinary catheter increases patient mobility and reduces the length of hospitalization. Early removal of the urinary catheter may be associated with postoperative urinary retention and recatheterization in a small number of patients.

Prescribe routinely scheduled acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs) and ketorolac. A key component of ERAS cesarean birth is the standardized administration of nonopioid pain medicines, alternating doses of acetaminophen and an NSAID. ERAS cesarean birth is likely to result in a reduction in inpatient and postdischarge opioid use.^22-24

VTE prophylaxis. Pneumatic compression stockings are recommended. Anticoagulation should not be routinely used for VTE prophylaxis.⁸

Auditing and reporting adherence with components of ERAS

In clinical practice there may be a gap between a clinician’s subjective perception of their performance and an independent audit of their clinical performance. ERAS pathways should be implemented with a commitment to performing audits and providing quantitative feedback to clinicians. Consistent use of measurement, feedback, and coaching can improve performance and reduce variation among individual clinicians. As an example, in one study of the use of a surgical safety checklist, 99% of the surgeons reported that they routinely used a surgical safety checklist, but the audit showed that the checklist was used in only 60% of cases.²⁵ Gaps between self-reported performance and audited performance are common in clinical practice. Audits with feedback are critical to improving adherence with the components of an ERAS pathway.

Three independent systematic reviews and meta-analyses report that ERAS pathways reduce hospital length of stay without increasing the readmission rate.^26-28 One meta-analysis reported that ERAS may also reduce time to first mobilization and result in earlier removal of the urinary catheter.²⁶ ERAS pathways also may reduce postoperative complications, lower pain scores, and decrease opioid use.²⁷ The general consensus among quality and safety experts is that reducing variation through standardization of pathways is generally associated with improved quality and enhanced safety. ERAS pathways have been widely accepted in multiple surgical fields. ERAS pathways should become the standard for performing cesarean procedures.●

EXPERT COMMENTARY

Sultan P, Bampoe S, Shah R, et al. Oral versus intravenous iron therapy for postpartum anemia: a systematic review and meta-analysis. Am J Obstet Gynecol. Published online December 19, 2018. DOI:10.1016/j.ajog.2018.12.016.

Iron deficiency anemia in pregnancy is associated with increased risk for adverse birth outcomes, including preterm delivery, cesarean delivery, and need for blood transfusion.^1,2 Although the outcomes with postpartum iron deficiency anemia are more difficult to study, this condition is associated with increased risk of maternal fatigue and depression, and it is often overlooked as a significant issue during the postpartum period.

In a recent systematic review, Sultan and colleagues sought to provide an updated assessment of IV versus oral iron treatment for postpartum anemia. The 6-week postpartum hemoglobin concentration was the primary outcome.

Details of the study

The authors screened 2,744 articles for randomized controlled trials (RCTs) comparing oral and IV iron in the treatment of postpartum anemia. Fifteen RCTs were included in the review, with 1,001 women receiving oral iron therapy and 1,181 women receiving IV iron. The baseline postpartum hemoglobin concentration in the 15 studies ranged from less than 8 g/dL to 10.5 g/dL.

In all but 1 study, the women in the IV treatment arm experienced a significant increase in postpartum hemoglobin concentration, with the mean difference being 1.0 g/dL at postpartum week 1 (95% confidence interval [CI], 0.5–1.5; P<.0001) and 0.9 g/dL at postpartum week 6 (95% CI, 0.4–1.3; P = .0003).

Only 4 studies were included in the meta-analysis; specifically, 6-week postpartum hemoglobin levels were measured in 251 women who received IV iron and in 134 who received oral iron. Significant differences were seen in the IV iron group compared with the oral iron group for 3 of the secondary outcomes evaluated: flushing (odds ratio [OR], 6.95), decreased constipation (OR, 0.08), and decreased dyspepsia (OR, 0.07).

None of the other secondary outcomes associated with IV iron (muscle cramps, headache, urticaria, rash, or anaphylaxis) occurred at statistically significant rates. Notably, adherence was not assessed in the majority of the studies. Although constipation was increased in the oral iron therapy group, it was reported at only 12%.

Study strengths and weaknesses

Results of this study support previous findings that IV iron is better tolerated, with fewer gastrointestinal adverse effects, than oral iron, and they re-emphasize that IV iron therapy is both safe (the authors identified only 2 cases of anaphylaxis) and effective in improving hematologic indices.

Continue to: The systematic review included...

The systematic review included studies, however, that excluded women treated for antepartum anemia, a group that may benefit from aggressive correction of iron deficiency. Another study weakness is that all the oral iron regimens used were dosed either daily or multiple times per day, which may lead to difficulty with adherence and can decrease overall iron absorption compared with an every-other-day regimen.³

Future studies are needed to determine 1) which women with what level of anemia will benefit the most from postpartum IV iron and 2) the hemoglobin level at which IV iron is a cost-effective therapy.

EXPERT COMMENTARY

Sultan P, Bampoe S, Shah R, et al. Oral versus intravenous iron therapy for postpartum anemia: a systematic review and meta-analysis. Am J Obstet Gynecol. Published online December 19, 2018. DOI:10.1016/j.ajog.2018.12.016.

Iron deficiency anemia in pregnancy is associated with increased risk for adverse birth outcomes, including preterm delivery, cesarean delivery, and need for blood transfusion.^1,2 Although the outcomes with postpartum iron deficiency anemia are more difficult to study, this condition is associated with increased risk of maternal fatigue and depression, and it is often overlooked as a significant issue during the postpartum period.

In a recent systematic review, Sultan and colleagues sought to provide an updated assessment of IV versus oral iron treatment for postpartum anemia. The 6-week postpartum hemoglobin concentration was the primary outcome.

Details of the study

The authors screened 2,744 articles for randomized controlled trials (RCTs) comparing oral and IV iron in the treatment of postpartum anemia. Fifteen RCTs were included in the review, with 1,001 women receiving oral iron therapy and 1,181 women receiving IV iron. The baseline postpartum hemoglobin concentration in the 15 studies ranged from less than 8 g/dL to 10.5 g/dL.

In all but 1 study, the women in the IV treatment arm experienced a significant increase in postpartum hemoglobin concentration, with the mean difference being 1.0 g/dL at postpartum week 1 (95% confidence interval [CI], 0.5–1.5; P<.0001) and 0.9 g/dL at postpartum week 6 (95% CI, 0.4–1.3; P = .0003).

Only 4 studies were included in the meta-analysis; specifically, 6-week postpartum hemoglobin levels were measured in 251 women who received IV iron and in 134 who received oral iron. Significant differences were seen in the IV iron group compared with the oral iron group for 3 of the secondary outcomes evaluated: flushing (odds ratio [OR], 6.95), decreased constipation (OR, 0.08), and decreased dyspepsia (OR, 0.07).

None of the other secondary outcomes associated with IV iron (muscle cramps, headache, urticaria, rash, or anaphylaxis) occurred at statistically significant rates. Notably, adherence was not assessed in the majority of the studies. Although constipation was increased in the oral iron therapy group, it was reported at only 12%.

Study strengths and weaknesses

Results of this study support previous findings that IV iron is better tolerated, with fewer gastrointestinal adverse effects, than oral iron, and they re-emphasize that IV iron therapy is both safe (the authors identified only 2 cases of anaphylaxis) and effective in improving hematologic indices.

Continue to: The systematic review included...

The systematic review included studies, however, that excluded women treated for antepartum anemia, a group that may benefit from aggressive correction of iron deficiency. Another study weakness is that all the oral iron regimens used were dosed either daily or multiple times per day, which may lead to difficulty with adherence and can decrease overall iron absorption compared with an every-other-day regimen.³

Future studies are needed to determine 1) which women with what level of anemia will benefit the most from postpartum IV iron and 2) the hemoglobin level at which IV iron is a cost-effective therapy.

EXPERT COMMENTARY

Sultan P, Bampoe S, Shah R, et al. Oral versus intravenous iron therapy for postpartum anemia: a systematic review and meta-analysis. Am J Obstet Gynecol. Published online December 19, 2018. DOI:10.1016/j.ajog.2018.12.016.

Iron deficiency anemia in pregnancy is associated with increased risk for adverse birth outcomes, including preterm delivery, cesarean delivery, and need for blood transfusion.^1,2 Although the outcomes with postpartum iron deficiency anemia are more difficult to study, this condition is associated with increased risk of maternal fatigue and depression, and it is often overlooked as a significant issue during the postpartum period.

In a recent systematic review, Sultan and colleagues sought to provide an updated assessment of IV versus oral iron treatment for postpartum anemia. The 6-week postpartum hemoglobin concentration was the primary outcome.

Details of the study

The authors screened 2,744 articles for randomized controlled trials (RCTs) comparing oral and IV iron in the treatment of postpartum anemia. Fifteen RCTs were included in the review, with 1,001 women receiving oral iron therapy and 1,181 women receiving IV iron. The baseline postpartum hemoglobin concentration in the 15 studies ranged from less than 8 g/dL to 10.5 g/dL.

In all but 1 study, the women in the IV treatment arm experienced a significant increase in postpartum hemoglobin concentration, with the mean difference being 1.0 g/dL at postpartum week 1 (95% confidence interval [CI], 0.5–1.5; P<.0001) and 0.9 g/dL at postpartum week 6 (95% CI, 0.4–1.3; P = .0003).

Only 4 studies were included in the meta-analysis; specifically, 6-week postpartum hemoglobin levels were measured in 251 women who received IV iron and in 134 who received oral iron. Significant differences were seen in the IV iron group compared with the oral iron group for 3 of the secondary outcomes evaluated: flushing (odds ratio [OR], 6.95), decreased constipation (OR, 0.08), and decreased dyspepsia (OR, 0.07).

None of the other secondary outcomes associated with IV iron (muscle cramps, headache, urticaria, rash, or anaphylaxis) occurred at statistically significant rates. Notably, adherence was not assessed in the majority of the studies. Although constipation was increased in the oral iron therapy group, it was reported at only 12%.

Study strengths and weaknesses

Results of this study support previous findings that IV iron is better tolerated, with fewer gastrointestinal adverse effects, than oral iron, and they re-emphasize that IV iron therapy is both safe (the authors identified only 2 cases of anaphylaxis) and effective in improving hematologic indices.

Continue to: The systematic review included...

The systematic review included studies, however, that excluded women treated for antepartum anemia, a group that may benefit from aggressive correction of iron deficiency. Another study weakness is that all the oral iron regimens used were dosed either daily or multiple times per day, which may lead to difficulty with adherence and can decrease overall iron absorption compared with an every-other-day regimen.³

Future studies are needed to determine 1) which women with what level of anemia will benefit the most from postpartum IV iron and 2) the hemoglobin level at which IV iron is a cost-effective therapy.

Illustration: Kimberly Martens for OBG Management

All mammalian life is dependent on a continuous supply of molecular oxygen. Molecular oxygen is carried to cells by noncovalent binding to the iron moiety in the hemoglobin of red blood cells. It is utilized within cells by noncovalent binding to the iron moiety in various microsomal and mitochondrial proteins, including myoglobin and cytochromes. Consequently, to efficiently utilize molecular oxygen all mammalian life is dependent on an adequate supply of iron. Surprisingly, in an era of high technology precision medicine, many pregnant women are iron deficient, anemic, and not receiving adequate iron supplementation.

Iron deficiency is prevalent in women and pregnant women

Women often become iron deficient because of pregnancy or heavy menstrual bleeding. During pregnancy, maternal iron is provided to supply the needs of the fetus and placenta. Additional iron is needed to expand maternal red blood cell volume and replace iron lost due to bleeding at delivery. In the National Health and Nutrition Examination Survey (NHANES) of 1988–1994, 11% of women aged 16 to 49 years were iron deficient. By contrast, less than 1% of men aged 16 to 49 years were iron deficient.¹

In a NHANES study from 1999–2006, risk factors for iron deficiency included multiparity, current pregnancy, and regular menstrual cycles. Use of hormonal contraception reduced the rate of iron deficiency.² Using the same data, the prevalences of iron deficiency during the first, second, and third trimesters of pregnancy were reported to be 7%, 14%, and 30%, respectively.³ In addition to pregnancy and menstrual bleeding there are many other medical problems that may contribute to iron deficiency, including Helicobacter pylori (H pylori) infection, gastritis, celiac disease, and bariatric surgery.

Iron deficiency anemia may be associated with adverse pregnancy outcomes

In a retrospective study of 75,660 singleton pregnancies, 7,977 women were diagnosed with iron deficiency anemia when they were admitted for delivery. Compared with pregnant women without iron deficiency, the presence of iron deficiency increased the risk of:

• blood transfusion (odds ratio [OR], 5.48; 95% confidence interval [CI], 4.57–6.58)
• preterm delivery (OR, 1.54; 95% CI, 1.36–1.76)
• cesarean delivery (OR, 1.30; 95% CI, 1.13–1.49)
• 5-minute Apgar score <7 (OR, 2.21; 95% CI, 1.84–2.64)
• intensive care unit (ICU) admission (OR, 1.28; 95% CI, 1.20–1.39).⁴

In a systematic review and meta-analysis of 26 studies, maternal anemia (mostly iron deficiency anemia) was associated with a higher risk of low birth weight (relative risk [RR], 1.31; 95% CI, 1.13–1.51), preterm birth (RR, 1.63; 95% CI, 1.33–2.01), perinatal mortality (RR, 1.51; 95% CI, 1.30–1.76), and neonatal mortality (RR, 2.72; 95% CI, 1.19–6.25).⁵

In a clinical trial, pregnant women were randomly assigned to receive folic acid alone; folic acid plus iron supplements; or 15 vitamins and minerals, including folic acid and iron. At delivery, women in the iron-folic acid and the 15 vitamin and minerals groups had higher hemoglobin concentrations than the folic acid monotherapy group. Among 4,697 live births, women in the iron-folic acid group had significantly fewer preterm births (<34 weeks’ gestation) than the folic acid group (RR, 0.50; 95% CI, 0.27–0.94; P = .031).⁶ Data from additional randomized trials are needed to further clarify the effect of iron supplementation on obstetric outcomes.

Related article:
Treating polycystic ovary syndrome: Start using dual medical therapy

The diagnosis of iron deficiency is optimized by measuring serum ferritin

Serum ferritin measurement is an excellent test of iron deficiency. We recommend that all pregnant women have serum ferritin measured at the first prenatal visit and at the beginning of the third trimester to assess maternal iron stores. In pregnancy, the Centers for Disease Control and Prevention and the World Health Organization define anemia as a hemoglobin level of less than 11 g/dL or hematocrit less than 33% in the first and third trimesters. If a pregnant woman is not anemic, a serum ferritin level less than 15 ng/mL indicates iron deficiency.⁷ Some experts believe that in pregnant women who are not anemic, a serum ferritin level between 15 and 30 ng/mL may also indicate iron deficiency.⁸ If the pregnant woman is anemic and does not have another cause of the anemia, a serum ferritin level less than 40 ng/mL is indicative of iron deficiency.⁷

Ferritin is an acute phase reactant and levels may be falsely elevated due to chronic or acute inflammation, liver disease, renal failure, metabolic syndrome, or malignancy. Some women with iron deficiency due to bariatric surgery or malabsorption also have vitamin B12 and, less commonly, folate deficiency, which can contribute to the development of anemia (see “Diagnosis of anemia, iron deficiency, and iron deficiency anemia in pregnancy.”) Clinicians are often advised that a mean corpuscular volume demonstrating microcytosis is the “best test” to assess a patient for iron deficiency. However, reduced iron availability and low ferritin precede microcytosis. Hence microcytosis is a lagging measure and iron deficiency is diagnosed at an earlier stage by ferritin.

Dietary iron

Iron in food is present in heme (meat, poultry, fish) and non-heme forms (grains, plant food, supplements). Heme iron is better absorbed than non-heme iron. Foods rich in non-heme iron include spinach, lentils, prune juice, dried prunes, and fortified cereals. Absorption of non-heme iron can be increased by vitamin C or vitamin C–rich foods (broccoli, bell peppers, cantaloupe, grapefruit, oranges, strawberries, and tomatoes). Absorption of non-heme iron is reduced by consumption of dairy products, coffee, tea, and chocolate.

Oral iron treatment

Oral iron is an effective treatment for iron deficiency^9,10 and is inexpensive, safe, and widely available. The CDC recommends that all pregnant women take a 30 mg/day iron supplement, unless they have hemochromatosis.¹¹ For women with a low ferritin level and anemia, iron supplementation should be increased to 30 to 120 mg daily.¹¹ Not all prenatal vitamins contain iron; those that do typically contain 17 to 28 mg of elemental iron per dose.

Many pregnant women taking oral iron, especially at doses greater than 30 mg daily, have gastrointestinal side effects, which cause them to discontinue the iron therapy.¹² Taking iron supplementation on an intermittent basis may help to reduce gastrointestinal side effects and improve iron stores.¹³

In the past, a standard approach to the treatment of iron deficiency anemia was oral ferrous sulfate 325 mg (65 mg elemental iron) spaced in 3 doses each day for a total daily dose of 195 mg elemental iron. However, recent absorption studies concluded that maximal absorption of iron occurs with a dose in the range of 40 to 80 mg of elemental iron daily. Greater doses do not result in more iron absorption and are associated with more side effects.^14,15 (See “Start using alternate-day oral iron dosing, and stop using daily iron dosing.”)

Oral iron should not be taken in close approximation to the consumption of milk, cereals, tea, coffee, eggs, or calcium supplements. The absorption of oral iron is enhanced by the consumption of orange juice or 250 mg of vitamin C. Gastrointestinal side effects include nausea, flatulence, constipation, diarrhea, epigastric distress, and vomiting. If gastrointestinal side effects occur, interventions that might improve tolerability include: reduce the dose of iron or administer intermittently or use a low dose of oral iron, where dosing can be more easily titrated.

We re-check ferritin and hemoglobin levels 2 to 4 weeks after initiation of oral iron therapy and expect to see a hemoglobin rise of 1 g/dL if the therapy is effective.

Intravenous iron treatment

For women with iron deficiency anemia who cannot tolerate oral iron or in whom oral iron treatment has not resolved their anemia, intravenous (IV) iron treatment may be an optimal approach. Women in the third trimester of pregnancy with iron deficiency anemia have very little time to consume sufficient quantities of oral iron in food and supplements to restore their deficiency and reverse their anemia. Consequently, treatment with IV iron may be especially appropriate for women with iron deficiency anemia in the third trimester of pregnancy. Prior gastric surgery, including gastric bypass, results in reduced gastric acid production and causes severe impairment of intestinal absorption of iron. Patients with malabsorption syndromes, including celiac disease, also may have limited absorption of oral iron. These populations of pregnant women may particularly benefit from the use of IV iron. In pregnant women IV iron has fewer gastrointestinal side effects than oral iron.¹⁶

Many severely iron deficient patients need 1,000 mg of iron to resolve their deficit. In order to avoid giving multiple standard doses (200 mg per infusion, with 5 infusions over many days), some centers have explored the use of 1 large dose of IV iron (1,000 mg of low molecular weight iron dextran administered over 1 hour) (INFeD, Watson Pharma).^17–19 This is not a regimen that is specifically approved by the US Food and Drug Administration. An alternative regimen is to administer 750 mg of ferrous carboxymaltose (Injectafer, Luitpold Pharmaceuticals) over 15 minutes, which is an FDA-approved regimen.¹⁸ Many hematologists prefer to administer multiple smaller doses of iron. For example, in our practice, pregnant women are commonly treated with IV iron sucrose (300 mg) every 2 weeks for 3 doses. To increase access of pregnant women to IV iron treatment, obstetricians need to work with hematologists and infusion centers to create collaborative protocols to expeditiously treat women in the third trimester.

There is an epidemic of iron deficiency in pregnant women in the United States. In an era of high technology medicine, it is surprising that iron deficiency remains an unsolved obstetric problem in our country.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Illustration: Kimberly Martens for OBG Management

All mammalian life is dependent on a continuous supply of molecular oxygen. Molecular oxygen is carried to cells by noncovalent binding to the iron moiety in the hemoglobin of red blood cells. It is utilized within cells by noncovalent binding to the iron moiety in various microsomal and mitochondrial proteins, including myoglobin and cytochromes. Consequently, to efficiently utilize molecular oxygen all mammalian life is dependent on an adequate supply of iron. Surprisingly, in an era of high technology precision medicine, many pregnant women are iron deficient, anemic, and not receiving adequate iron supplementation.

Iron deficiency is prevalent in women and pregnant women

Women often become iron deficient because of pregnancy or heavy menstrual bleeding. During pregnancy, maternal iron is provided to supply the needs of the fetus and placenta. Additional iron is needed to expand maternal red blood cell volume and replace iron lost due to bleeding at delivery. In the National Health and Nutrition Examination Survey (NHANES) of 1988–1994, 11% of women aged 16 to 49 years were iron deficient. By contrast, less than 1% of men aged 16 to 49 years were iron deficient.¹

In a NHANES study from 1999–2006, risk factors for iron deficiency included multiparity, current pregnancy, and regular menstrual cycles. Use of hormonal contraception reduced the rate of iron deficiency.² Using the same data, the prevalences of iron deficiency during the first, second, and third trimesters of pregnancy were reported to be 7%, 14%, and 30%, respectively.³ In addition to pregnancy and menstrual bleeding there are many other medical problems that may contribute to iron deficiency, including Helicobacter pylori (H pylori) infection, gastritis, celiac disease, and bariatric surgery.

Iron deficiency anemia may be associated with adverse pregnancy outcomes

In a retrospective study of 75,660 singleton pregnancies, 7,977 women were diagnosed with iron deficiency anemia when they were admitted for delivery. Compared with pregnant women without iron deficiency, the presence of iron deficiency increased the risk of:

• blood transfusion (odds ratio [OR], 5.48; 95% confidence interval [CI], 4.57–6.58)
• preterm delivery (OR, 1.54; 95% CI, 1.36–1.76)
• cesarean delivery (OR, 1.30; 95% CI, 1.13–1.49)
• 5-minute Apgar score <7 (OR, 2.21; 95% CI, 1.84–2.64)
• intensive care unit (ICU) admission (OR, 1.28; 95% CI, 1.20–1.39).⁴

In a systematic review and meta-analysis of 26 studies, maternal anemia (mostly iron deficiency anemia) was associated with a higher risk of low birth weight (relative risk [RR], 1.31; 95% CI, 1.13–1.51), preterm birth (RR, 1.63; 95% CI, 1.33–2.01), perinatal mortality (RR, 1.51; 95% CI, 1.30–1.76), and neonatal mortality (RR, 2.72; 95% CI, 1.19–6.25).⁵

In a clinical trial, pregnant women were randomly assigned to receive folic acid alone; folic acid plus iron supplements; or 15 vitamins and minerals, including folic acid and iron. At delivery, women in the iron-folic acid and the 15 vitamin and minerals groups had higher hemoglobin concentrations than the folic acid monotherapy group. Among 4,697 live births, women in the iron-folic acid group had significantly fewer preterm births (<34 weeks’ gestation) than the folic acid group (RR, 0.50; 95% CI, 0.27–0.94; P = .031).⁶ Data from additional randomized trials are needed to further clarify the effect of iron supplementation on obstetric outcomes.

Related article:
Treating polycystic ovary syndrome: Start using dual medical therapy

The diagnosis of iron deficiency is optimized by measuring serum ferritin

Serum ferritin measurement is an excellent test of iron deficiency. We recommend that all pregnant women have serum ferritin measured at the first prenatal visit and at the beginning of the third trimester to assess maternal iron stores. In pregnancy, the Centers for Disease Control and Prevention and the World Health Organization define anemia as a hemoglobin level of less than 11 g/dL or hematocrit less than 33% in the first and third trimesters. If a pregnant woman is not anemic, a serum ferritin level less than 15 ng/mL indicates iron deficiency.⁷ Some experts believe that in pregnant women who are not anemic, a serum ferritin level between 15 and 30 ng/mL may also indicate iron deficiency.⁸ If the pregnant woman is anemic and does not have another cause of the anemia, a serum ferritin level less than 40 ng/mL is indicative of iron deficiency.⁷

Ferritin is an acute phase reactant and levels may be falsely elevated due to chronic or acute inflammation, liver disease, renal failure, metabolic syndrome, or malignancy. Some women with iron deficiency due to bariatric surgery or malabsorption also have vitamin B12 and, less commonly, folate deficiency, which can contribute to the development of anemia (see “Diagnosis of anemia, iron deficiency, and iron deficiency anemia in pregnancy.”) Clinicians are often advised that a mean corpuscular volume demonstrating microcytosis is the “best test” to assess a patient for iron deficiency. However, reduced iron availability and low ferritin precede microcytosis. Hence microcytosis is a lagging measure and iron deficiency is diagnosed at an earlier stage by ferritin.

Dietary iron

Iron in food is present in heme (meat, poultry, fish) and non-heme forms (grains, plant food, supplements). Heme iron is better absorbed than non-heme iron. Foods rich in non-heme iron include spinach, lentils, prune juice, dried prunes, and fortified cereals. Absorption of non-heme iron can be increased by vitamin C or vitamin C–rich foods (broccoli, bell peppers, cantaloupe, grapefruit, oranges, strawberries, and tomatoes). Absorption of non-heme iron is reduced by consumption of dairy products, coffee, tea, and chocolate.

Oral iron treatment

Oral iron is an effective treatment for iron deficiency^9,10 and is inexpensive, safe, and widely available. The CDC recommends that all pregnant women take a 30 mg/day iron supplement, unless they have hemochromatosis.¹¹ For women with a low ferritin level and anemia, iron supplementation should be increased to 30 to 120 mg daily.¹¹ Not all prenatal vitamins contain iron; those that do typically contain 17 to 28 mg of elemental iron per dose.

Many pregnant women taking oral iron, especially at doses greater than 30 mg daily, have gastrointestinal side effects, which cause them to discontinue the iron therapy.¹² Taking iron supplementation on an intermittent basis may help to reduce gastrointestinal side effects and improve iron stores.¹³

In the past, a standard approach to the treatment of iron deficiency anemia was oral ferrous sulfate 325 mg (65 mg elemental iron) spaced in 3 doses each day for a total daily dose of 195 mg elemental iron. However, recent absorption studies concluded that maximal absorption of iron occurs with a dose in the range of 40 to 80 mg of elemental iron daily. Greater doses do not result in more iron absorption and are associated with more side effects.^14,15 (See “Start using alternate-day oral iron dosing, and stop using daily iron dosing.”)

Oral iron should not be taken in close approximation to the consumption of milk, cereals, tea, coffee, eggs, or calcium supplements. The absorption of oral iron is enhanced by the consumption of orange juice or 250 mg of vitamin C. Gastrointestinal side effects include nausea, flatulence, constipation, diarrhea, epigastric distress, and vomiting. If gastrointestinal side effects occur, interventions that might improve tolerability include: reduce the dose of iron or administer intermittently or use a low dose of oral iron, where dosing can be more easily titrated.

We re-check ferritin and hemoglobin levels 2 to 4 weeks after initiation of oral iron therapy and expect to see a hemoglobin rise of 1 g/dL if the therapy is effective.

Intravenous iron treatment

For women with iron deficiency anemia who cannot tolerate oral iron or in whom oral iron treatment has not resolved their anemia, intravenous (IV) iron treatment may be an optimal approach. Women in the third trimester of pregnancy with iron deficiency anemia have very little time to consume sufficient quantities of oral iron in food and supplements to restore their deficiency and reverse their anemia. Consequently, treatment with IV iron may be especially appropriate for women with iron deficiency anemia in the third trimester of pregnancy. Prior gastric surgery, including gastric bypass, results in reduced gastric acid production and causes severe impairment of intestinal absorption of iron. Patients with malabsorption syndromes, including celiac disease, also may have limited absorption of oral iron. These populations of pregnant women may particularly benefit from the use of IV iron. In pregnant women IV iron has fewer gastrointestinal side effects than oral iron.¹⁶

Many severely iron deficient patients need 1,000 mg of iron to resolve their deficit. In order to avoid giving multiple standard doses (200 mg per infusion, with 5 infusions over many days), some centers have explored the use of 1 large dose of IV iron (1,000 mg of low molecular weight iron dextran administered over 1 hour) (INFeD, Watson Pharma).^17–19 This is not a regimen that is specifically approved by the US Food and Drug Administration. An alternative regimen is to administer 750 mg of ferrous carboxymaltose (Injectafer, Luitpold Pharmaceuticals) over 15 minutes, which is an FDA-approved regimen.¹⁸ Many hematologists prefer to administer multiple smaller doses of iron. For example, in our practice, pregnant women are commonly treated with IV iron sucrose (300 mg) every 2 weeks for 3 doses. To increase access of pregnant women to IV iron treatment, obstetricians need to work with hematologists and infusion centers to create collaborative protocols to expeditiously treat women in the third trimester.

There is an epidemic of iron deficiency in pregnant women in the United States. In an era of high technology medicine, it is surprising that iron deficiency remains an unsolved obstetric problem in our country.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Illustration: Kimberly Martens for OBG Management

All mammalian life is dependent on a continuous supply of molecular oxygen. Molecular oxygen is carried to cells by noncovalent binding to the iron moiety in the hemoglobin of red blood cells. It is utilized within cells by noncovalent binding to the iron moiety in various microsomal and mitochondrial proteins, including myoglobin and cytochromes. Consequently, to efficiently utilize molecular oxygen all mammalian life is dependent on an adequate supply of iron. Surprisingly, in an era of high technology precision medicine, many pregnant women are iron deficient, anemic, and not receiving adequate iron supplementation.

Iron deficiency is prevalent in women and pregnant women

Women often become iron deficient because of pregnancy or heavy menstrual bleeding. During pregnancy, maternal iron is provided to supply the needs of the fetus and placenta. Additional iron is needed to expand maternal red blood cell volume and replace iron lost due to bleeding at delivery. In the National Health and Nutrition Examination Survey (NHANES) of 1988–1994, 11% of women aged 16 to 49 years were iron deficient. By contrast, less than 1% of men aged 16 to 49 years were iron deficient.¹

In a NHANES study from 1999–2006, risk factors for iron deficiency included multiparity, current pregnancy, and regular menstrual cycles. Use of hormonal contraception reduced the rate of iron deficiency.² Using the same data, the prevalences of iron deficiency during the first, second, and third trimesters of pregnancy were reported to be 7%, 14%, and 30%, respectively.³ In addition to pregnancy and menstrual bleeding there are many other medical problems that may contribute to iron deficiency, including Helicobacter pylori (H pylori) infection, gastritis, celiac disease, and bariatric surgery.

Iron deficiency anemia may be associated with adverse pregnancy outcomes

In a retrospective study of 75,660 singleton pregnancies, 7,977 women were diagnosed with iron deficiency anemia when they were admitted for delivery. Compared with pregnant women without iron deficiency, the presence of iron deficiency increased the risk of:

• blood transfusion (odds ratio [OR], 5.48; 95% confidence interval [CI], 4.57–6.58)
• preterm delivery (OR, 1.54; 95% CI, 1.36–1.76)
• cesarean delivery (OR, 1.30; 95% CI, 1.13–1.49)
• 5-minute Apgar score <7 (OR, 2.21; 95% CI, 1.84–2.64)
• intensive care unit (ICU) admission (OR, 1.28; 95% CI, 1.20–1.39).⁴

In a systematic review and meta-analysis of 26 studies, maternal anemia (mostly iron deficiency anemia) was associated with a higher risk of low birth weight (relative risk [RR], 1.31; 95% CI, 1.13–1.51), preterm birth (RR, 1.63; 95% CI, 1.33–2.01), perinatal mortality (RR, 1.51; 95% CI, 1.30–1.76), and neonatal mortality (RR, 2.72; 95% CI, 1.19–6.25).⁵

In a clinical trial, pregnant women were randomly assigned to receive folic acid alone; folic acid plus iron supplements; or 15 vitamins and minerals, including folic acid and iron. At delivery, women in the iron-folic acid and the 15 vitamin and minerals groups had higher hemoglobin concentrations than the folic acid monotherapy group. Among 4,697 live births, women in the iron-folic acid group had significantly fewer preterm births (<34 weeks’ gestation) than the folic acid group (RR, 0.50; 95% CI, 0.27–0.94; P = .031).⁶ Data from additional randomized trials are needed to further clarify the effect of iron supplementation on obstetric outcomes.

Related article:
Treating polycystic ovary syndrome: Start using dual medical therapy

The diagnosis of iron deficiency is optimized by measuring serum ferritin

Serum ferritin measurement is an excellent test of iron deficiency. We recommend that all pregnant women have serum ferritin measured at the first prenatal visit and at the beginning of the third trimester to assess maternal iron stores. In pregnancy, the Centers for Disease Control and Prevention and the World Health Organization define anemia as a hemoglobin level of less than 11 g/dL or hematocrit less than 33% in the first and third trimesters. If a pregnant woman is not anemic, a serum ferritin level less than 15 ng/mL indicates iron deficiency.⁷ Some experts believe that in pregnant women who are not anemic, a serum ferritin level between 15 and 30 ng/mL may also indicate iron deficiency.⁸ If the pregnant woman is anemic and does not have another cause of the anemia, a serum ferritin level less than 40 ng/mL is indicative of iron deficiency.⁷

Ferritin is an acute phase reactant and levels may be falsely elevated due to chronic or acute inflammation, liver disease, renal failure, metabolic syndrome, or malignancy. Some women with iron deficiency due to bariatric surgery or malabsorption also have vitamin B12 and, less commonly, folate deficiency, which can contribute to the development of anemia (see “Diagnosis of anemia, iron deficiency, and iron deficiency anemia in pregnancy.”) Clinicians are often advised that a mean corpuscular volume demonstrating microcytosis is the “best test” to assess a patient for iron deficiency. However, reduced iron availability and low ferritin precede microcytosis. Hence microcytosis is a lagging measure and iron deficiency is diagnosed at an earlier stage by ferritin.

Dietary iron

Iron in food is present in heme (meat, poultry, fish) and non-heme forms (grains, plant food, supplements). Heme iron is better absorbed than non-heme iron. Foods rich in non-heme iron include spinach, lentils, prune juice, dried prunes, and fortified cereals. Absorption of non-heme iron can be increased by vitamin C or vitamin C–rich foods (broccoli, bell peppers, cantaloupe, grapefruit, oranges, strawberries, and tomatoes). Absorption of non-heme iron is reduced by consumption of dairy products, coffee, tea, and chocolate.

Oral iron treatment

Oral iron is an effective treatment for iron deficiency^9,10 and is inexpensive, safe, and widely available. The CDC recommends that all pregnant women take a 30 mg/day iron supplement, unless they have hemochromatosis.¹¹ For women with a low ferritin level and anemia, iron supplementation should be increased to 30 to 120 mg daily.¹¹ Not all prenatal vitamins contain iron; those that do typically contain 17 to 28 mg of elemental iron per dose.

Many pregnant women taking oral iron, especially at doses greater than 30 mg daily, have gastrointestinal side effects, which cause them to discontinue the iron therapy.¹² Taking iron supplementation on an intermittent basis may help to reduce gastrointestinal side effects and improve iron stores.¹³

In the past, a standard approach to the treatment of iron deficiency anemia was oral ferrous sulfate 325 mg (65 mg elemental iron) spaced in 3 doses each day for a total daily dose of 195 mg elemental iron. However, recent absorption studies concluded that maximal absorption of iron occurs with a dose in the range of 40 to 80 mg of elemental iron daily. Greater doses do not result in more iron absorption and are associated with more side effects.^14,15 (See “Start using alternate-day oral iron dosing, and stop using daily iron dosing.”)

Oral iron should not be taken in close approximation to the consumption of milk, cereals, tea, coffee, eggs, or calcium supplements. The absorption of oral iron is enhanced by the consumption of orange juice or 250 mg of vitamin C. Gastrointestinal side effects include nausea, flatulence, constipation, diarrhea, epigastric distress, and vomiting. If gastrointestinal side effects occur, interventions that might improve tolerability include: reduce the dose of iron or administer intermittently or use a low dose of oral iron, where dosing can be more easily titrated.

We re-check ferritin and hemoglobin levels 2 to 4 weeks after initiation of oral iron therapy and expect to see a hemoglobin rise of 1 g/dL if the therapy is effective.

Intravenous iron treatment

For women with iron deficiency anemia who cannot tolerate oral iron or in whom oral iron treatment has not resolved their anemia, intravenous (IV) iron treatment may be an optimal approach. Women in the third trimester of pregnancy with iron deficiency anemia have very little time to consume sufficient quantities of oral iron in food and supplements to restore their deficiency and reverse their anemia. Consequently, treatment with IV iron may be especially appropriate for women with iron deficiency anemia in the third trimester of pregnancy. Prior gastric surgery, including gastric bypass, results in reduced gastric acid production and causes severe impairment of intestinal absorption of iron. Patients with malabsorption syndromes, including celiac disease, also may have limited absorption of oral iron. These populations of pregnant women may particularly benefit from the use of IV iron. In pregnant women IV iron has fewer gastrointestinal side effects than oral iron.¹⁶

Many severely iron deficient patients need 1,000 mg of iron to resolve their deficit. In order to avoid giving multiple standard doses (200 mg per infusion, with 5 infusions over many days), some centers have explored the use of 1 large dose of IV iron (1,000 mg of low molecular weight iron dextran administered over 1 hour) (INFeD, Watson Pharma).^17–19 This is not a regimen that is specifically approved by the US Food and Drug Administration. An alternative regimen is to administer 750 mg of ferrous carboxymaltose (Injectafer, Luitpold Pharmaceuticals) over 15 minutes, which is an FDA-approved regimen.¹⁸ Many hematologists prefer to administer multiple smaller doses of iron. For example, in our practice, pregnant women are commonly treated with IV iron sucrose (300 mg) every 2 weeks for 3 doses. To increase access of pregnant women to IV iron treatment, obstetricians need to work with hematologists and infusion centers to create collaborative protocols to expeditiously treat women in the third trimester.

There is an epidemic of iron deficiency in pregnant women in the United States. In an era of high technology medicine, it is surprising that iron deficiency remains an unsolved obstetric problem in our country.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.