Abstract
Purpose of Review
The purpose of this study was to define maternal critical illness (MCI) and outline its causes, the tools used to identify it, and current treatment recommendations.
Recent Findings
Although MCI is uncommon, it comprises >10% of intensive care (ICU) admissions in women aged <50 years. Of critically ill mothers, 1:20 die. Almost half these deaths are preventable. Monitoring should follow convention, yet MCI is often treated outside ICUs. Patient youth and the relative rarity of MCI often lead to underestimation of risk and delays in care. Imaging is underutilized. There is no information regarding mechanical ventilation targets. Data regarding drug safety is derived from non-critically ill pregnant women and from retrospective case-control studies which often overestimate risk.
Summary
MCI is accompanied by significant excess mortality. Imaging studies, treatments, or medication should not be withheld from cases of MCI solely due to concerns regarding fetal outcome. There remain important knowledge gaps in both diagnosis and treatment of MCI.
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Introduction
Maternal critical illness (MCI) is a relatively new field of intensive care. Like other rare diseases, MCI is difficult to study. Hesitance to include pregnant women in clinical trials has delayed research on this population; in response, the National Institutes Health Office of Research on Women’s Health has begun to encourage inclusion of pregnant women in clinical trials [1]. Recent years have seen a surge of interest in the health of pregnant women and, within this framework, in MCI. This review discusses the definitions of MCI, its causes, and the tools used to identify it; it summarizes current information regarding monitoring and treatment of this population and points to existing knowledge gaps that require attention in future research.
Definition of Maternal Critical Illness
Maternal critical illness can be described using disease-specific criteria (e.g., hemorrhage, pre-eclampsia), organ-specific criteria (e.g., renal failure, heart failure), or treatment criteria (e.g., the need for ventilation, the need for ICU admission).
Epidemiology
Inconsistent definition is a major obstacle when determining the epidemiology of MCI [2•, 3•]. Maternal ICU admission (which differs from MCI) occurs in approximately 1:300 deliveries (290–330:100,000) (Table 1). While these rates are not particularly high, this cohort represents 12.1% of the women aged 16–50 years admitted to adult general ICUs [4••]. In developed countries, the rate of peripartum maternal death approximates 8.5–14:100,000 deliveries [5,6,7•]; therefore, one maternal death occurs approximately among every 20 maternal ICU admissions (Table 1).
The young age of the population suffering from MCI and the relative rarity of MCI often lead to underestimation of risk. “Approximately one quarter of women requiring high dependency unit care ‘lie beneath’ the criteria for near miss or severe maternal complications” [8]. As a result, treatment that would normally have been provided in an ICU is often provided elsewhere. When cases treated outside the ICU are included in MCI cohorts, the true proportion of mothers at risk rises to 1200/100,000 deliveries (1.2%) [9].
The definition of the “peripartum” period is an additional confounder. Many population-based studies of maternal death, for example, describe only cases occurring during admission for delivery [6, 7•]. Pregnancy-related diseases are not necessarily associated with delivery and may even manifest outside arbitrarily defined “peripartum” time frames after pregnancy. For example, postpartum cardiomyopathy was defined in the past as heart failure developing between the last month of pregnancy and the first 5 months after delivery [10]. Concerns regarding possible under-diagnosis even within this broad time frame led to a change in definition to include the more lenient period “from the end of pregnancy to the months following delivery” [11]. Expanding the peripartum period to pregnancy “within the past year” has almost doubled the captured incidence of maternal mortality [12].
Identifying the Women at Risk
Most maternal deaths during the peripartum period occur due to intrapartum and postpartum hemorrhage, complications of hypertensive disease of pregnancy, infections, and exacerbation of pre-existing medical conditions (e.g., heart disease) [7•, 13••]. Reports of peripartum maternal complications show a similar case mix [9, 14•]. Several risk factors have been associated with these complications, including pregnancy at a later age [15, 16], multiparity [15, 17] assisted conception [17, 18], obesity [19], and possibly cesarean delivery [20].
Almost 40% of pregnancy-related deaths are potentially preventable [13••, 21, 22]. Worldwide, the most striking finding in reports of MCI is the presence of delays in care [23,24,25,26]. Apparently, identifying the risk factors associated with maternal complications in clinical studies is much easier than identifying deterioration in a specific parturient.
During hemorrhage, for example, patient vital signs are the tools used to determine patient condition. However, apart from the normal variability in the physiological response to hemorrhage, several physiological changes of pregnancy render the consequences of hemorrhage even more unpredictable during pregnancy. These include increased blood volume and decreased hematocrit yielding baseline anemia, decreased systolic blood pressure accompanied by increased heart rate secondary to reduced systemic vascular resistance, and increased respiratory rate [27]. The presence of maternal comorbidities such as diabetes and hypertension complicate diagnosis even further.
Maternal sepsis remains a lead cause of maternal mortality worldwide [5, 28]. The incidence of severe maternal sepsis seems to be on the rise [29, 30]. However, most tools fail to identify sepsis in obstetric populations [31, 32]. A meta-analysis of the physiological indicators commonly used to diagnose the presence of sepsis demonstrated that current knowledge regarding the normal range of these parameters during pregnancy and the peripartum period is based on observations from only a handful of studies. Furthermore, values considered normal during pregnancy and the peripartum period thoroughly overlap with the values normally used to diagnose the presence of sepsis [33••] (Table 2). This overlap precludes the use of standard early warning scores (EWS) for alerting medical staff to the presence of sepsis in the peripartum period.
This problem has prompted the development of modified early warning scores (MEWS) for the pregnant population [35•]. However, the MEWS was derived retrospectively from the vital signs of ICU obstetric admissions rather than prospectively from a full cohort of pregnant and peripartum cases. Furthermore, at this time, only one study has actually demonstrated a reduction in severe maternal morbidity after implementing the use of a MEWS [36••]; it is unclear whether this study was confounded by the Hawthorne effect.
Pre-Emptive Treatment
Most causes of maternal death and critical illness are amenable to treatment even before ICU admission. In case of hemorrhage, early identification of ongoing bleeding is crucial. Uterotonic agents must be administered immediately postpartum to all women regardless of route of delivery or parturient location. [37]. Oxytocin (intravenous or intramuscular) is the drug of choice. Ongoing hemorrhage beyond 30 min calls first for addition of synthetic PGE2, then for other medical treatments [e.g., carboprost (15-methyl PGF2), methylergometrine, misoprostol (PGE1)] in parallel to other definitive treatments of hemorrhage. Hemorrhage must be treated aggressively with blood (in accordance with massive transfusion protocols), non-surgical interventions (e.g., uterine packing, balloon tamponade, angio-embolization), and timely definitive surgery when required [38•]. Several guidelines have been published for treatment of maternal hemorrhage.
Women with severe hypertensive disease of pregnancy or pre-eclampsia should be tightly monitored and their blood pressure kept below 160/100 mmHg [39]. Severely elevated blood pressures have been associated with increased risk of end organ damage (e.g., stroke, myocardial infarction, renal failure) and death [40]. Antihypertensive medications such as specific beta and calcium channel inhibitors, diazoxide, and sodium nitroprusside may assist in blood pressure control [41]. Magnesium sulfate remains a mainstay of treatment for seizure prophylaxis [42]; two controlled trials have established its superiority in reducing the risk of eclampsia compared to anticonvulsants [43, 44]. Atypical eclampsia, development of focal neurologic signs, and/or prolonged unconsciousness require urgent neuroimaging [45].
Diagnosis of peripartum infection demands a high index of suspicion. However, “[a]ntibiotic prescription for pregnant or postpartum women with suspected infection does not necessarily prevent progression to severe sepsis, which may be rapidly progressive.” [46]. Therefore, once infection is suspected, the threshold for ICU admission should be low, and monitoring and supportive care should be initiated as soon as possible.
A similarly high index of suspicion is required to diagnose cardiomyopathy of pregnancy. Maternal prognosis has been associated with the severity of heart failure [47]. Depending on underlying etiology, it is thus reasonable to assume that commencing treatment of heart failure early (and thereby unloading the strain on the left heart) may be associated with better maternal outcome. Pre-existing heart disease often exacerbates during pregnancy. Appropriate cardiac care throughout pregnancy and timely anesthesia assessment and preparation may result in better management of delivery and a smaller number of complications, although this has yet to be proven.
Finally, guidelines for venous thromboprophylaxis may easily be implemented and have been shown to systematically reduce maternal death rates [48••].
Monitoring
Once MCI has been identified, hemodynamic monitoring should generally follow convention. When in doubt, the clinician should prioritize the balance between the potential risk and the benefit to the mother, rather than the potential risk to the fetus versus the benefit to the mother.
Central Venous Pressure
The value of central vein monitoring for guiding fluid therapy remains questionable in most patients [49] and is no different in pregnancy. Early studies showing poor correlation between central venous and pulmonary capillary wedge pressures have led to disenchantment with both these tools for assessing fluid responsiveness in pre-eclampsia [50, 51]. Although standard operating procedures often recommend insertion of a CVP for guiding fluid management in pre-eclampsia, most professionals treating this population do not consider this tool particularly useful [52•].
Pulmonary Capillary Wedge Pressure Monitoring
There is a relatively high complication rate among women undergoing pulmonary artery catheterization in the peripartum period (∼4%), probably due to increased hypercoagulability and susceptibility to infection [53]. Insertion of a pulmonary artery catheter should therefore be restricted to specific cases of severe maternal hypertension, pulmonary vascular disease, and/or heart failure.
Dynamic Measures of Fluid Responsiveness
There is little to no literature regarding the value of using dynamic measures (e.g., pulse pressure variation, stroke volume variation) to guide fluid therapy in the peripartum period. A search of the literature disclosed only one study comparing goal-directed fluid therapy using the LiDCO system during elective Caesarian delivery in 100 parturients with hypertensive disease. The control (unmonitored) group received less fluids and more phenylephrine and had somewhat poorer neonatal outcomes [54].
Impedance Cardiography
This tool has been proposed for hemodynamic measurement during pregnancy because it is non-invasive, user-friendly, and requires little training. However, the accuracy of impedance cardiography in measuring cardiac output and stroke volume remains controversial even in non-pregnant populations. The few studies that have examined the validity of impedance cardiography during the paripartum period present conflicting results; some show good correlation between impedance measurements and other traditional measurement methods [55, 56] and others do not [57, 58]. Therefore, at this point, there is insufficient data to recommend this monitoring technique.
Echocardiography
Bedside transthoracic echocardiography (TTE) has become entrenched in the management of critically ill patients and is similarly valuable in pregnancy [59•]. It may be used to identify the presence of pulmonary hypertension and/or right ventricular failure in pulmonary embolism (i.e., venous thromboembolic phenomena, amniotic fluid embolism), to differentiate between cardiomyopathy and severe hypertensive disease of pregnancy with left ventricular heart failure [60], to assess fluid responsiveness in the presence of severe pre-eclampsia [61], and to detect poor ventricular filling in septic or hemorrhagic shock. A meta-analysis of data from a prospective study and the existing literature comparing cardiac output measured by TTE with that measured using the pulmonary artery catheter in pregnant women with complications demonstrated excellent agreement [62].
Imaging
Due to their low risk profile, ultrasonography and magnetic resonance imaging (MRI) are preferred over imaging techniques requiring ionizing radiation, provided they are sufficiently informative. However, if indicated, there is no justification for withholding diagnostic imaging from the mother due to concerns regarding their safety for the fetus. One study recently demonstrated that only 18.8% of obstetric patients admitted after involvement in high-risk motor vehicle accidents underwent appropriate imaging studies [63•].
Fetal risk from ionizing radiation depends on the dose of radiation and the gestational age of the fetus at the time of exposure [64]. Low-exposure imaging radiography tests include cervical spine and extremity radiography (about 0.001 mGy each) and chest radiography (0.01 mGy). Medium-exposure imaging includes computed tomography (CT) of the chest (0.66 mGy) and high-exposure tests include lumbar spine imaging and CT of the head or neck (about 10 mGy), abdomen (>35 mGy), and pelvis (50 mGy) [65].
Maternal exposure to radiation is accompanied by three types of risk: miscarriage, fetal growth retardation, and fetal teratogenesis. Teratogenesis is by far the greatest concern and occurs mainly during the first trimester of pregnancy. In general, exposure to <0.5 Gy is accompanied by a very small risk of teratogenicity in early pregnancy. Doses >0.5 Gy require risk assessment. Still, in absolute terms, the overall risk remains low (1:250) [65].
General Treatment Principles
Several principles should underlie any decision made by clinicians concerning treatment of critically ill pregnant women. First, maternal welfare must be prioritized over that of the fetus. Thus, no imaging study, treatment, or medication should be withheld from the pregnant ICU patient if it is necessary for her well-being [66].
The second principle is that pregnancy is not the same throughout the trimesters. Embryogenesis is mostly complete by the end of the first trimester. Therefore, malformations are significantly less likely to occur after this period. Information regarding the safety profile of some medications during pregnancy (e.g., antibiotics, antihypertensive medications, and magnesium sulfate) is mostly derived from women who were not critically ill. Retrospective case-control studies, which are most commonly used to asses maternal exposure, tend to overestimate the risk of malformation [67]. Information regarding the risk of drug administration is best derived from prospective registries when available [e.g., the Norwegian Mother and Child registry (MoBa), Swedish Medical Birth Register and Danish National Birth Cohort (DNBC)].
Finally, most treatment provided in the ICU is supportive (i.e., intended to prevent injury and sustain basic life functions rather than treat the underlying cause of disease). Therefore, the benefit provided by any treatment should surpass the damage it may incur.
Airway Management and Ventilation
The rate of ventilator support among women admitted to an ICU in the peripartum period ranges between 13.6 and 58%, probably reflecting variability in case mix as well as practice [68, 69]. Some claim that non-invasive ventilation is generally not recommended during pregnancy due to an increased risk of aspiration in the presence of delayed gastric emptying [70]. However, among the pregnant patients who needed assisted ventilation in an ICU, one fourth to one fifth have received non-invasive ventilation with no untoward effect [71].
Intubation of a pregnant woman should be approached as if it were a known difficult intubation [72•, 73, 74]. Pregnancy is accompanied by increased airway edema and weight gain, both of which obscure the view of the vocal cords. This is further complicated by a lower functional residual capacity, relative dyspnea, and an increase in oxygen consumption, which lead to shorter times to desaturation in pregnancy [27]. If the patient is a priori hypoxemic or in shock, this leaves no leeway for mistakes. Precisely for this reason, intubation should not be unnecessarily postponed—it is best performed under controlled conditions by an experienced operator.
After intubation, debate surrounds target respiratory endpoints. Normal pregnancy is accompanied by tachypnea and respiratory alkalosis. Some recommend that minute ventilation be adjusted to maintain PaCO2 between 30 and 32 mmHg. However, this recommendation is not supported by evidence and must therefore be weighed against the potential damage caused by cerebral vasoconstriction.
Regarding oxygenation, the maternal oxyhemoglobin dissociation curve shifts to the right during pregnancy (P50 increases from 27 to 30 mmHg). A higher partial pressure of oxygen is therefore required to achieve the same maternal oxygen saturation. While there is no justification for administration of more oxygen than recommended for most critically ill patients, it is imperative to tightly follow maternal blood gases and lactate levels to ensure the presence of adequate tissue perfusion and oxygenation.
Conversely, the fetal oxyhemoglobin dissociation curve shifts to the left (P50 is 19 mmHg), conferring relative resilience to hypoxia. Because both utero-placental circulation and pre-fetal oxygen consumption by the placenta may limit the availability of oxygen to the fetus, this increase in fractional extraction during acute hypoxia creates a reserve capacity, allowing the fetus to tolerate up to a 50% reduction in oxygen delivery. During sustained hypoxia (e.g., severe maternal hypoxemia), this mechanism will lead to slowing of fetal growth, as oxygen consumption remains unchanged when corrected for fetal mass [75].
Medications
The drugs administered to women admitted to the ICU in the peripartum period are intended to prevent complications or treat the underlying cause of admission.
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Vasopressors and inotropes: Norepinephrine and epinephrine are endogenous catecholamines, which make any relationship between exogenous administration of these drugs and adverse pregnancy outcomes difficult to determine. Furthermore, both drugs are used only during severe MCI, which in itself is associated with fetal risk. Norepinephrine is classified as FDA category C, the assumption being that the detrimental effect of placental vasoconstriction may be balanced by the benefit of decreasing hypoperfusion. Both epinephrine and norepinephrine cross the placenta, but controversy remains regarding their effect on the fetus. The clinician must judge whether maternal condition requires administration of these drugs or if an equally effective treatment alternative exists.
Data regarding ephedrine and phenylephrine (both second-line drugs for hemodynamic support in MCI) are mostly derived from their use during regional anesthesia for cesarean delivery. Ephedrine does not decrease the utero-placental circulation [76] but may be associated with fetal acidosis [77•]. Phenylephrine has been associated with increased maternal bradycardia [77•].
Dopamine, another endogenous catecholamine (classified as FDA category C), has been used in low doses (1–5 mcg/kg/min) to increase urine output women with oliguria and pre-eclampsia without untoward effects [78]. However, dopamine has been associated with more adverse events (particularly maternal arrythmias) than noradrenalin when used to treat septic shock in the general population [79].
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Pain control and sedation: Maternal pain thresholds are significantly increased during pregnancy [80]; even more so during labor in term pregnancy [81]. Although maternal blood volume is increased [27], so is maternal sympathetic tone and venous return to the heart [82]. This combination may result in an increased susceptibility to the hemodynamic side effects of analgesic drugs.
Opioids generally cross the placenta; nonetheless, they remain the mainstay of sedation and pain treatment in pregnancy. Remifentanyl is the analgesic of choice for long-term sedation due to its ultra-short metabolism. Natural opiates (e.g., morphine, codeine) have safety risk profiles in terms of teratogenicity. Some uncertainty still exists regarding whether synthetic opioids (e.g., fentanyl, tramadol) are associated with cardiovascular and neural tube defects [83]. Should delivery occur during critical illness, it is important to remember that opioids used in proximity to delivery may cause fetal respiratory depression; the presence of a neonatologist on location is thus crucial. Benzodiazepines should only be considered in unique circumstances given the overall increasing preference towards use of drugs other than benzodiazepines in the ICU as well as the controversy regarding the association of drugs from this family with congenital anomalies [84, 85].
The concentration of albumin is lower in fetal than in maternal serum during the first half of pregnancy. Propofol binds almost completely to albumin. Moreover, the pharmacodynamics of propofol are stable throughout pregnancy [86]; during brief exposure to propofol, the fluid cavities surrounding the developing embryo do not act as a reservoir for this drug; thus, maternal serum concentration of propofol is always higher than fetal serum concentration [87]. Although data regarding longer sedation periods with propofol is limited to case reports, the FDA final rule does not forbid the use of this drug.
Non-steroidal antiinflammatory drugs (NSAIDs) should be avoided during the first and third trimester of pregnancy. During the first trimester, use of NSAIDs has been associated with fetal congenital heart defects and increased risk of miscarriage. During the third trimester, NSAID use may cause premature closure of the ductus arteriosus and fetal distress [88].
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Muscle relaxants: Muscle relaxants are used to overcome patient-ventilator asynchrony in severely hypoxemic patients. Indications for administration of neuromuscular blockers in critically ill pregnant women are similar to those in the general population. In the presence of convulsions (e.g., eclampsia), the use of muscle relaxants is not recommended; there is significant concern that the presence of ongoing convulsions will be masked, leading to risk of increased neurological damage.
Short-acting muscle relaxants (e.g., Rocuronium, Atracurium) are generally preferred over long-acting muscle relaxants. Muscle relaxants may cause relatively prolonged maternal neuro-muscular blockade at term or in the postpartum period [89]. Muscle relaxants also partly cross the placenta which may induce neuromuscular blockade in the neonate [90].
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Stress ulcer prophylaxis: Administration of therapy for prevention of stress ulcers is one of the less controversial recommendations for critically ill patients [91]. Proton pump inhibitors (PPIs) are preferred as they significantly reduce the risk of both clinically important and overt GI bleeding compared to histamine-2-receptor antagonists (H2RA) [92]. Both PPIs and H2RAs are considered safe throughout pregnancy [93, 94].
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Prophylaxis of deep venous thrombosis (VTE): Women who are admitted to the ICU should be considered candidates for VTE prophylaxis [95, 96]. Apart from the increased risk of hypercoagulability inherent to pregnancy [27], most maternal ICU admissions occur postpartum [4••] and many arrive after cesarean delivery. Both of these are significant risk factors for occurrence of VTE [97, 98].
Anticoagulation therapy may consist of either unfractionated heparin or low-molecular weight heparin. Neither crosses the placenta nor enters breast milk and both are considered safe [99•]. There is limited evidence regarding the safety of newer anticoagulants, and they should therefore be avoided during pregnancy unless alternative; safer options are contraindicated (e.g., in the presence of heparin-induced thrombocytopenia).
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Antibiotic therapy: penicillins, cephalosporins, and macrolides have been used for decades and are classified as FDA pregnancy category B. Trimethoprim-sulfamethoxazole and tetracyclines are classified as FDA category D drugs and should therefore be avoided during pregnancy unless there is no other treatment choice (i.e., maternal benefit overshadows fetal risk). Both have been associated with teratogenicity and neonatal morbidity. Fluoroquinolones have been associated with fetal cartilage damage and arthropathies but are classified nevertheless as category C based on accumulating evidence from both animal studies and clinical experience of safety during pregnancy [100].
Unique Obstetric Considerations
Nutrition
The caloric requirements of the human fetus is about 90–100 kcal/kg/day at term [101]. There is therefore no need to increase the caloric intake of the critically ill pregnant patient by more than 500 kcal/day, unless the patient was undernourished prior to ICU admission. Lactation is associated with an increase in energy expenditure of approximately 10–15% [102]. The energy loss incurred by lactation is met mostly by fat loss rather than protein loss [102, 103]. However, maternal high-fat diet has recently been associated with worse neurological outcomes in animal models of hypoxic-ischemic encephalopathy [104] and may affect the microbiome of the neonate [105]. Maternal glucose supplementation is also damaging, leading to fetal programming towards metabolic syndrome [106]. To conclude, pregnancy and lactation require little caloric expenditure. Maternal overfeeding and/or supplementation of maternal diet with specific nutritional components may be accompanied by a range of adverse fetal effects. Nutrition of the critically ill mother should not deviate from standard practice in terms of both total caloric intake and composition.
Breast Engorgement
Postpartum breast engorgement may occur despite the presence of MCI. Symptoms include tight, painful breasts, and elevated body temperature, usually occurring on postpartum days 2–5. Treatment of breast engorgement has been anecdotal thus far; there is insufficient evidence to justify widespread implementation of any intervention for either preventing or treating breast engorgement [107].
Delivery Planning
Mode and timing of delivery should both be determined by maternal benefit and relevant obstetrical indications. Almost half of the pregnancies involving MCI result in preterm delivery (gestational age <37 weeks) [108]. If the pregnancy endangers the mother, her well-being should be prioritized and delivery should occur regardless of gestational age. Otherwise, if possible, the pregnancy may be carried to term. Ideally, early preterm delivery (gestational age <34 weeks) should occur in a tertiary care center with expertise in maternal-fetal medicine, obstetric anesthesia, and neonatal intensive care.
The accepted limit of neonatal viability describes the period between 20 + 0/7 weeks and 25 + 6/7 weeks of gestation [109], prior to which neonatal monitoring is not indicated. Once gestational age has progressed beyond 24 weeks, monitoring per obstetrician recommendation (e.g., with non-stress test or ultrasound and biophysical profile) should be performed. Neonatal outcome may be improved by antenatal maternal administration of corticosteroids and/or magnesium sulfate for fetus’ <34 weeks gestation. A 2-day antenatal corticosteroid course effectively promotes fetal lung maturation (betamethasone 12 mg ×1/day or dexamethasone 6 mg ×4/day) [109]. Neonatal benefit from such treatment must always be weighed against the risk of increased maternal susceptibility to infection. At a gestational age <30 weeks, antenatal maternal treatment with magnesium sulfate within 6 h of delivery may also improve neonatal neurological outcome [109].
Conclusion
The definition of MCI must be standardized to elucidate the prevalence of this clinical condition and its causes. MCI is accompanied by significant excess mortality, perhaps in part due to differential treatment of MCI compared to critical illness in other populations (e.g., within versus outside the ICU). No imaging study, treatment, or medication deemed necessary for the mother’s safety or well-being should be withheld in MCI due to concerns regarding fetal outcome. When deciding on treatment, the good of the mother should always outweigh any considerations regarding pregnancy outcome. There remain important knowledge gaps regarding identification and treatment (e.g., mechanical ventilation, drugs) of MCI.
References
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Blehar MC, Spong C, Grady C, Goldkind SF, Sahin L, Clayton JA. Enrolling pregnant women: issues in clinical research. Womens Health Issues. 2013;23(1):e39–45. doi:10.1016/j.whi.2012.10.003.
• Van Parys AS, Verstraelen H, Roelens K, Temmerman M. Maternal intensive care: a systematic literature review. Facts Views Vis Obgyn. 2010;2(3):161–7. There is no standard definition for maternal intensive care.
• Tunçalp O, Hindin MJ, Souza JP, Chou D, Say L. The prevalence of maternal near miss: a systematic review. BJOG. 2012;119(6):653–61. doi:10.1111/j.1471-0528.2012.03294.x. Maternal death constitutes the tip of the iceberg. The real issue is maternal critical illness which occurs at much higher rates and is often missed.
•• Intensive Care National Audit and Research Centre (ICNARC). Female admissions (aged 16–50) to adult, general critical care units in England, Wales and Northern Ireland reported as ‘currently pregnant’ or ‘recently pregnant’. ICNARC, 2013. https://www.oaa-anaes.ac.uk/assets/_managed/cms/files/Obstetric%20admissions%20to%20critical%20care%202009–2012%20-%20FINAL.pdf (Accessed 29th April 2016). MCIs comprise >10% of ICU admissions in women aged <50 years. MCI is often treated outside the ICU.
Knight M, Kenyon S, Brocklehurst P, Neilson J, Shakespeare J, Kurinczuk JJ, editors. On behalf of MBRRACE-UK. Saving lives, improving mothers’ care—lessons learned to inform future maternity care from the UK and Ireland confidential enquiries into maternal deaths and morbidity 2009–12. Oxford: National Perinatal Epidemiology Unit, University of Oxford; 2014.
Lisonkova S, Liu S, Bartholomew S, Liston RM. Joseph KS; Maternal Health Study Group of the Canadian Perinatal Surveillance System. Temporal trends in maternal mortality in Canada II: estimates based on hospitalization data. J Obstet Gynaecol Can. 2011;33(10):1020–30.
• Mhyre JM, Tsen LC, Einav S, Kuklina EV, Leffert LR, Bateman BT. Cardiac arrest during hospitalization for delivery in the United States, 1998-2011. Anesthesiology. 2014;120(4):810–8. The main causes of maternal death are hemorrhage, heart disease (primary and secondary), sepsis, thromboembolism, and hypertensive disease complications
O'Malley EG, Popivanov P, Fergus A, Tan T, Byrne B. Maternal near miss: what lies beneath? Eur J Obstet Gynecol Reprod Biol. 2016;199:116–20. doi:10.1016/j.ejogrb.2016.01.031.
Royal College of Obstetricians and Gynaecologists. Providing equity of critical and maternal care for the critically ill pregnant or recently pregnant women. Maternal Critical Care Working Group, 2011. https://www.rcog.org.uk/globalassets/documents/guidelines/prov_eq_matandcritcare.pdf).
Pearson GD, Veille JC, Rahimtoola S, Hsia J, Oakley CM, Hosenpud JD, Ansari A, Baughman KL. Peripartum cardiomyopathy: National Heart, Lung, and Blood Institute and Office of Rare Diseases (National Institutes of Health) workshop recommendations and review. JAMA. 2000;283:1183–8.
Sliwa K, Hilfiker-Kleiner D, Petrie MC, Mebazaa A, Pieske B, Buchmann E, Regitz-Zagrosek V, Schaufelberger M, Tavazzi L, van Veldhuisen DJ, Watkins H, Shah AJ, Seferovic PM, Elkayam U, Pankuweit S, Papp Z, Mouquet F, McMurray JJ, Heart Failure Association of the European Society of Cardiology Working Group on Peripartum Cardiomyopathy. Current state of knowledge on aetiology, diagnosis, management, and therapy of peripartum cardiomyopathy: a position statement from the Heart Failure Association of the European Society of Cardiology Working Group on peripartum cardiomyopathy. Eur J Heart Fail. 2010;12:767–78.
Fine Maron D. Has maternal mortality really doubled in the US? Scientific American. 2015 Jun. Accessed at: http://www.scientificamerican.com/article/has-maternal-mortality-really-doubled-in-the-u-s/.
•• Berg CJ, Harper MA, Atkinson SM, Bell EA, Brown HL, Hage ML, Mitra AG, Moise Jr KJ, Callaghan WM. Preventability of pregnancy-related deaths: results of a state-wide review. Obstet Gynecol. 2005;106(6):1228–34. Forty percent of pregnancy-related deaths in California were potentially preventable
• Pollock W, Rose L, Dennis CL. Pregnant and postpartum admissions to the intensive care unit: a systematic review. Intensive Care Med. 2010;36(9):1465–74. doi:10.1007/s00134-010-1951-0. The common causes of maternal ICU admission are similar to those of maternal ICU death but their relative proportions are slightly different
Luke B, Brown MB. Elevated risks of pregnancy complications and adverse outcomes with increasing maternal age. Hum Reprod. 2007;22(5):1264–72.
Blomberg M, Birch Tyrberg R, Kjølhede P. Impact of maternal age on obstetric and neonatal outcome with emphasis on primiparous adolescents and older women: a Swedish Medical Birth Register Study. BMJ Open. 2014;4(11):e005840.
Martin AS, Monsour M, Kissin DM, Jamieson DJ, Callaghan WM, Boulet SL. Trends in severe maternal morbidity after assisted reproductive technology in the United States, 2008-2012. Obstet Gynecol. 2016;127(1):59–66.
Qin J, Liu X, Sheng X, Wang H, Gao S. Assisted reproductive technology and the risk of pregnancy-related complications and adverse pregnancy outcomes in singleton pregnancies: a meta-analysis of cohort studies. Fertil Steril. 2016;105(1):73–85. e1-6
Young OM, Twedt R, Catov JM. Pre-pregnancy maternal obesity and the risk of preterm preeclampsia in the American primigravida. Obesity (Silver Spring). 2016;24(6):1226–9. doi:10.1002/oby.21412.
Esteves-Pereira AP, Deneux-Tharaux C, Nakamura-Pereira M, Saucedo M, Bouvier-Colle MH, Leal MC. Caesarean delivery and postpartum maternal mortality: a population-based case control study in Brazil. PLoS One. 2016;11(4):e0153396. doi:10.1371/journal.pone.0153396. eCollection 2016
De La Rosa K, Mhyre J, Anderson FW. Maternal mortality from hemorrhage in Michigan 1998-2011 [8]. Obstet Gynecol. 2016;127(Suppl 1):3S. doi:10.1097/01.AOG.0000483624.54449.84.
Hasegawa J, Sekizawa A, Tanaka H, Katsuragi S, Osato K, Murakoshi T, Nakata M, Nakamura M, Yoshimatsu J, Sadahiro T, Kanayama N, Ishiwata I, Kinoshita K, Ikeda T, Maternal Death Exploratory Committee in Japan; Japan Association of Obstetricians and Gynecologists. Current status of pregnancy-related maternal mortality in Japan: a report from the Maternal Death Exploratory Committee in Japan. BMJ Open. 2016;6(3):e010304. doi:10.1136/bmjopen-2015-010304.
Amaral E, Souza JP, Surita F, Luz AG, Sousa MH, Cecatti JG, Campbell O. A population-based surveillance study on severe acute maternal morbidity (near-miss) and adverse perinatal outcomes in Campinas, Brazil: the Vigimoma project. BMC Pregnancy Childbirth. 2011;11:9. doi:10.1186/1471-2393-11-9.
Martijn L, Jacobs A, Amelink-Verburg M, Wentzel R, Buitendijk S, Wensing M. Adverse outcomes in maternity care for women with a low risk profile in The Netherlands: a case series analysis. BMC Pregnancy Childbirth. 2013;13:219. doi:10.1186/1471-2393-13-219.
Bonnet MP, Deneux-Tharaux C, Bouvier-Colle MH. Critical care and transfusion management in maternal deaths from postpartum haemorrhage. Eur J Obstet Gynecol Reprod Biol. 2011;158(2):183–8. doi:10.1016/j.ejogrb.2011.04.042.
Bauer ME, Lorenz RP, Bauer ST, Rao K, Anderson FW. Maternal deaths due to sepsis in the state of Michigan, 1999-2006. Obstet Gynecol. 2015;126(4):747–52. doi:10.1097/AOG.0000000000001028.
Tan EK, Tan EL. Alterations in physiology and anatomy during pregnancy. Best Pract Res Clin Obstet Gynaecol. 2013;27(6):791–802. doi:10.1016/j.bpobgyn.2013.08.001.
Fernández-Pérez ER, Salman S, Pendem S, Farmer JC. Sepsis during pregnancy. Crit Care Med. 2005;33(10 Suppl):S286–93.
Bauer ME, Bateman BT, Bauer ST, Shanks AM, Mhyre JM. Maternal sepsis mortality and morbidity during hospitalization for delivery: temporal trends and independent associations for severe sepsis. Anesth Analg. 2013;117(4):944–50.
Acosta CD, Knight M, Lee HC, Kurinczuk JJ, Gould JB, Lyndon A. The continuum of maternal sepsis severity: incidence and risk factors in a population-based cohort study. PLoS One. 2013;8:e67175.
Lappen JR, Keene M, Lore M, Grobman WA, Gossett DR. Existing models fail to predict sepsis in an obstetric population with intrauterine infection. Am J Obstet Gynecol. 2010;203(6):573. doi:10.1016/j.ajog.2010.07.040.e1-5
Maguire PJ, Power KA, Downey AF, O'Higgins AC, Sheehan SR, Turner MJ. Evaluation of the systemic inflammatory response syndrome criteria for the diagnosis of sepsis due to maternal bacteremia. Int J Gynaecol Obstet. 2016;133(1):116–9. doi:10.1016/j.ijgo.2015.09.017.
•• Bauer ME, Bauer ST, Rajala B, MacEachern MP, Polley LS, Childers D, Aronoff DM. Maternal physiologic parameters in relationship to systemic inflammatory response syndrome criteria: a systematic review and meta-analysis. Obstet Gynecol. 2014;124(3):535–41. doi:10.1097/AOG.0000000000000423. SIRS criteria for diagnosis of sepsis overlap with the normal range of the same parameters during pregnancy, limiting our ability to diagnose sepsis in this population.
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016;315(8):801–10.
• Carle C, Alexander P, Columb M, Johal J. Design and internal validation of an obstetric early warning score: secondary analysis of the Intensive Care National Audit and Research Centre Case Mix Programme database. Anaesthesia. 2013;68(4):354–67. doi:10.1111/anae.12180. Development and validation of a modified early warning score intended for the maternal population.
•• Shields LE, Wiesner S, Klein C, Pelletreau B, Hedriana HL. Use of maternal early warning trigger tool reduces maternal morbidity. Am J Obstet Gynecol. 2016;214(4):527.e1–6. doi:10.1016/j.ajog.2016.01.154. External validation of the modified early warning score. Use of this score may improve maternal outcomes.
Sentilhes L, Vayssière C, Deneux-Tharaux C, Aya AG, Bayoumeu F, Bonnet MP, Djoudi R, Dolley P, Dreyfus M, Ducroux-Schouwey C, Dupont C, François A, Gallot D, Haumonté JB, Huissoud C, Kayem G, Keita H, Langer B, Mignon A, Morel O, Parant O, Pelage JP, Phan E, Rossignol M, Tessier V, Mercier FJ, Goffinet F. Postpartum hemorrhage: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF): in collaboration with the French Society of Anesthesiology and Intensive Care (SFAR). Eur J Obstet Gynecol Reprod Biol. 2016;198:12–21.
• Dahlke JD, Mendez-Figueroa H, Maggio L, Hauspurg A, Sperling JD, Chauhan SP, Rouse DJ. Prevention and management of postpartum hemorrhage: a comparison of 4 national guidelines. Am J Obstet Gynecol. 2015;213(1):76.e1–10. doi:10.1016/j.ajog.2015.02.023. Although the need to follow protocol during maternal massive transfusion in maternal hemorrhage has been recognized, considerable variability still exists between protocols.
American College of Obstetricians and Gynecologists, Task Force on Hypertension in Pregnancy, Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ task force on hypertension in pregnancy. Obstet Gynecol. 2013;122(5):1122–31.
Vidaeff AC, Carroll MA, Ramin SM. Acute hypertensive emergencies in pregnancy. Crit Care Med. 2005;33(10):S307–12.
Ronsmans C, Campbell O. Quantifying the fall in mortality associated with interventions related to hypertensive diseases of pregnancy. BMC Public Health. 2011;11(Suppl 3):S8. doi:10.1186/1471-2458-11-S3-S8.
Berhan Y, Berhan A. Should magnesium sulfate be administered to women with mild pre-eclampsia? A systematic review of published reports on eclampsia. J Obstet Gynaecol Res. 2015;41:831–42.
Lucas MJ, Leveno KJ, Cunningham FG. A comparison of magnesium sulfate with phenytoin for the prevention of eclampsia. N Engl J Med. 1995;333:201–5.
[No authors listed]. Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet 1995;345(8963):1455–63.
Edlow JA, Caplan LR, O’Brien K, Tibbles CD. Diagnosis of acute neurological emergencies in pregnant and post-partum women. Lancet Neurol. 2013;12:175–85.
Knight M, Acosta C, Brocklehurst P, Cheshire A, Fitzpatrick K, Hinton L, Jokinen M, Kemp B, Kurinczuk JJ, Lewis G, Lindquist A, Locock L, Nair M, Patel N,Quigley M, Ridge D, Rivero-Arias O, Sellers S, Shah A. Beyond maternal death: improving the quality of maternal care through national studies of ‘near-miss’ maternal morbidity. Southampton (UK): NIHR Journals Library; 2016 Jun. Programme Grants for Applied Research.
McNamara DM, Elkayam U, Alharethi R, Damp J, Hsich E, Ewald G, Modi K, Alexis JD, Ramani GV, Semigran MJ, Haythe J, Markham DW, Marek J, Gorcsan 3rd J, Wu WC, Lin Y, Halder I, Pisarcik J, Cooper LT, Fett JD, IPAC Investigators. Clinical outcomes for peripartum cardiomyopathy in North America: results of the IPAC study (Investigations of Pregnancy-Associated Cardiomyopathy). J Am Coll Cardiol. 2015;66(8):905–14. doi:10.1016/j.jacc.2015.06.1309.
•• Friedman AM, D'Alton ME. Venous thromboembolism bundle: risk assessment and prophylaxis for obstetric patients. Semin Perinatol. 2016;40(2):87–92. doi:10.1053/j.semperi.2015.11.012. Prophylaxis of thromboembolism reduces maternal death rate. Recommendations for such prophylaxis are presented.
Marik PE, Baram M, Vahid B. Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares. Chest. 2008;134(1):172–8.
Bolte AC, Dekker GA, van Eyck J, van Schijndel RS, van Geijn HP. Lack of agreement between central venous pressure and pulmonary capillary wedge pressure in preeclampsia. Hypertens Pregnancy. 2000;19(3):261–71.
Tellez R, Curiel R. Relationship between central venous pressure and pulmonary capillary wedge pressure in severely toxemic patients. Am J Obstet Gynecol. 1991;165(2):487.
• Rucklidge MW, Hughes RD. Central venous pressure monitoring in severe preeclampsia: a survey of UK practice. Int J Obstet Anesth. 2011;20(3):274. doi:10.1016/j.ijoa.2011.04.001. Most standard operating procedures recommend insertion of a CVP for guiding fluid management in pre-eclampsia, but professionals treating this population do not consider this tool useful.
Gilbert WM, Towner DR, Field NT, Anthony J. The safety and utility of pulmonary artery catheterization in severe preeclampsia and eclampsia. Am J Obstet Gynecol. 2000;182(6):1397–403.
Xiao W, Duan Q, Zhao L, Chi X, Wang F, Ma D, Wang T. Goal-directed fluid therapy may improve hemodynamic stability in parturient women under combined spinal epidural anesthesia for cesarean section and newborn well-being. J Obstet Gynaecol Res. 2015;41:1547–55.
Burlingame J, Ohana P, Aaronoff M, Seto T. Noninvasive cardiac monitoring in pregnancy: impedance cardiography versus echocardiography. J Perinatol. 2013;33(9):675–80.
Masaki DI, Greenspoon JS, Ouzounian JG. Measurement of cardiac output in pregnancy by thoracic electrical bioimpedance and thermodilution. A preliminary report. Am J Obstet Gynecol. 1989;161:680–4.
McIntyre JP, Ellyett KM, Mitchell EA, Quill GM, Thompson JM, Stewart AW, Doughty RN, Stone PR, Maternal Sleep in Pregnancy Study Group. Validation of thoracic impedance cardiography by echocardiography in healthy late pregnancy. BMC Pregnancy Childbirth. 2015;15:70.
Moertl MG, Schlembach D, Papousek I, Hinghofer-Szalkay H, Weiss EM, Lang U, Lackner HK. Hemodynamic evaluation in pregnancy: limitations of impedance cardiography. Physiol Meas. 2012;33(6):1015–26.
• Dennis AT. Transthoracic echocardiography in obstetric anaesthesia and obstetric critical illness. Int J Obstet Anesth. 2011;20(2):160–8. An excellent review of the uses of transthoracic echocardiography in management of MCI and barriers to implementation to such use.
Ntusi NB, Badri M, Gumedze F, Sliwa K, Mayosi BM. Pregnancy-associated heart failure: a comparison of clinical presentation and outcome between hypertensive heart failure of pregnancy and idiopathic peripartum cardiomyopathy. PLoS One. 2015;10(8):e0133466. doi:10.1371/journal.pone.0133466. eCollection 2015
Brun C, Zieleskiewicz L, Textoris J, Muller L, Bellefleur JP, Antonini F, Tourret M, Ortega D, Vellin A, Lefrant JY, Boubli L, Bretelle F, Martin C, Leone M. Prediction of fluid responsiveness in severe preeclamptic patients with oliguria. Intensive Care Med. 2013;39(4):593–600. doi:10.1007/s00134-012-2770-2.
Cornette J, Laker S, Jeffery B, Lombaard H, Alberts A, Rizopoulos D, Roos-Hesselink JW, Pattinson RC. Validation of maternal cardiac output assessed by transthoracic echocardiography against pulmonary artery catheters in severely ill pregnant women. A prospective comparative study and systematic review. Ultrasound Obstet Gynecol. 2016; doi:10.1002/uog.16015.
• Shakerian R, Thomson BN, Judson R, Skandarajah AR. Radiation fear: impact on compliance with trauma imaging guidelines in the pregnant patient. J Trauma Acute Care Surg. 2015;78(1):88–93. Pregnant women do not undergo appropriate imaging workup after trauma.
American College of Radiology. ACR–SPR practice parameter for imaging pregnant or potentially pregnant adolescents and women with ionizing radiation. Resolution 39. Reston (VA): ACR; 2014.
Tremblay E, Thérasse E, Thomassin-Naggara I, Trop I. Quality initiatives: guidelines for use of medical imaging during pregnancy and lactation. Radiographics. 2012;32:897–911.
American College of Obstetricians and Gynecologists. Practice bulletin no. 158: critical care in pregnancy. Obstet Gynecol. 2016;127(1):e21–8.
McNutt LA, Wu C, Xue X, Hafner JP. Estimating the relative risk in cohort studies and clinical trials of common outcomes. Am J Epidemiol. 2003;157(10):940–3.
Rios FG, Risso-Vázquez A, Alvarez J, Vinzio M, Falbo P, Rondinelli N, Bienzobas DH. Clinical characteristics and outcomes of obstetric patients admitted to the intensive care unit. Int J Gynaecol Obstet. 2012;119(2):136–40. doi:10.1016/j.ijgo.2012.05.039.
Leung NY, Lau AC, Chan KK, Yan WW. Clinical characteristics and outcomes of obstetric patients admitted to the intensive care unit: a 10-year retrospective review. Hong Kong Med J. 2010;16:18–25.
American Society of Anesthesiologists Task Force on Obstetric Anesthesia. Practice guidelines for obstetric anesthesia: an updated report by the American Society of Anesthesiologists Task Force on Obstetric Anesthesia. Anesthesiology. 2007;106:843–6.
Seppänen P, Sund R, Roos M, Unkila R, Meriläinen M, Helminen M, Ala-Kokko T, Suominen T. Obstetric admissions to ICUs in Finland: a multicentre study. Intensive Crit Care Nurs. 2016;35:38–44. doi:10.1016/j.iccn.2016.03.002.
• McKeen DM, George RB, O'Connell CM, Allen VM, Yazer M, Wilson M, Phu TC. Difficult and failed intubation: incident rates and maternal, obstetrical, and anesthetic predictors. Can J Anaesth. 2011;58:514–24. Difficult intubation may be encountered in 5–6% of pregnant women, justifying maternal airway management by experts in this field.
Quinn AC, Milne D, Columb M, Gorton H, Knight M. Failed tracheal intubation in obstetric anaesthesia: 2 yr national case-control study in the UK. Br J Anaesth. 2013;110(1):74–80. doi:10.1093/bja/aes320.
Kinsella SM, Winton AL, Mushambi MC, Ramaswamy K, Swales H, Quinn AC, Popat M. Failed tracheal intubation during obstetric general anaesthesia: a literature review. Int J Obstet Anesth. 2015;24(4):356–74.
Carter AM. Placental gas exchange and the oxygen supply to the fetus. Compr Physiol. 2015;5(3):1381–403.
Minzter BH, Johnson RF, Paschall RL, Ramasubramanian R, Ayers GD, Downing JW. The diverse effects of vasopressors on the fetoplacental circulation of the dual perfused human placenta. Anesth Analg. 2010;110(3):857–62.
• Veeser M, Hofmann T, Roth R, Klöhr S, Rossaint R, Heesen M. Vasopressors for the management of hypotension after spinal anesthesia for elective caesarean section. Systematic review and cumulative meta-analysis. Acta Anaesthesiol Scand. 2012;56(7):810–6. Ephedrine, but not phenylephrine, has been associated with fetal acidosis. Phenylephrine has been associated with more reflexive maternal bradycardia.
Kirshon B, Lee W, Mauer MB, Cotton DB. Effects of low-dose dopamine therapy in the oliguric patient with preeclampsia. Am J Obstet Gynecol. 1988;159:604–7.
de Backer D, Biston P, Devriendt J, Madl C, Chochrad D, Aldecoa C, Brasseur A, Defrance P, Gottignies P, Vincent JL, SOAP II Investigators. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010;362(9):779–89.
Draisci G, Catarci S, Vollono C, Zanfini BA, Pazzaglia C, Cadeddu C, Virdis D, Valeriani M. Pregnancy-induced analgesia: a combined psychophysical and neurophysiological study. Eur J Pain. 2012;16(10):1389–97.
Ohel I, Walfisch A, Shitenberg D, Sheiner E, Hallak M. A rise in pain threshold during labor: a prospective clinical trial. Pain. 2007;132(Suppl 1):S104–8.
Ouzounian JG, Elkayam U. Physiologic changes during normal pregnancy and delivery. Cardiol Clin. 2012;30(3):317–29.
Källén B, Reis M. Ongoing pharmacological management of chronic pain in pregnancy. Drugs. 2016;76(9):915–24. doi:10.1007/s40265-016-0582-3.
Fraser GL, Devlin JW, Worby CP, Alhazzani W, Barr J, Dasta JF, Kress JP, Davidson JE, Spencer FA. Benzodiazepine versus nonbenzodiazepine-based sedation for mechanically ventilated, critically ill adults: a systematic review and meta-analysis of randomized trials. Crit Care Med. 2013;41(9 Suppl 1):S30–8. doi:10.1097/CCM.0b013e3182a16898.
Wikner BN, Stiller CO, Bergman U, Asker C, Källén B. Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: neonatal outcome and congenital malformations. Pharmacoepidemiol Drug Saf. 2007;16(11):1203–10.
Ragno G, Cicinelli E, Schonauer S, Vetuschi C. Propofol assay in biological fluids in pregnant women. J Pharm Biomed Anal. 1997;15(11):1633–40.
Jauniaux E, Gulbis B, Shannon C, Maes V, Bromley L, Rodeck C. Placental propofol transfer and fetal sedation during maternal general anaesthesia in early pregnancy. Lancet. 1998;352(9124):290–1.
Bloor M, Paech M. Nonsteroidal anti-inflammatory drugs during pregnancy and the initiation of lactation. Anesth Analg. 2013;116(5):1063–75.
Pühringer FK, Sparr HJ, Mitterschiffthaler G, Agoston S, Benzer A. Extended duration of action of rocuronium in postpartum patients. Anesth Analg. 1997;84(2):352–4.
Guay J, Grenier Y, Varin F. Clinical pharmacokinetics of neuromuscular relaxants in pregnancy. Clin Pharmacokinet. 1998;34(6):483.
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R, Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580–637.
Alshamsi F, Belley-Cote E, Cook D, Almenawer SA, Alqahtani Z, Perri D, Thabane L, Al-Omari A, Lewis K, Guyatt G, Alhazzani W. Efficacy and safety of proton pump inhibitors for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis of randomized trials. Crit Care. 2016;20(1):120.
Gill SK, O'Brien L, Koren G. The safety of histamine 2 (H2) blockers in pregnancy: a meta-analysis. Dig Dis Sci. 2009;54(9):1835–8.
Gill SK, O'Brien L, Einarson TR, Koren G. The safety of proton pump inhibitors (PPIs) in pregnancy: a meta-analysis. Am J Gastroenterol. 2009;104(6):1541–5.
Chan WS, Rey E, Kent NE, VTE in Pregnancy Guideline Working Group, Chan WS, Kent NE, Rey E, Corbett T, David M, Douglas MJ, Gibson PS, Magee L, Rodger M, Smith RE, Society of Obstetricians and Gynecologists of Canada. Venous thromboembolism and antithrombotic therapy in pregnancy. J Obstet Gynaecol Can. 2014;36(6):527–53.
Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO, American College of Chest Physicians. VTE, thrombophilia, antithrombotic therapy and pregnancy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e691S–736S. doi:10.1378/chest.11-2300.
Meng K, Hu X, Peng X, Zhang Z. Incidence of venous thromboembolism during pregnancy and the puerperium: a systematic review and meta-analysis. J Matern Fetal Neonatal Med. 2015;28(3):245–53. doi:10.3109/14767058.2014.913130.
Blondon M, Casini A, Hoppe KK, Boehlen F, Righini M, Smith NL. Risks of venous thromboembolism after cesarean sections: a meta-analysis. Chest. 2016; doi:10.1016/j.chest.2016.05.021.
• Romualdi E, Dentali F, Rancan E, Squizzato A, Steidl L, Middeldorp S, Ageno W. Anticoagulant therapy for venous thromboembolism during pregnancy: a systematic review and a meta-analysis of the literature. J Thromb Haemost. 2013;11:270–81. Low molecular weight heparin is both safe and effective for thromboprophylaxis during pregnancy.
Yefet E, Salim R, Chazan B, Akel H, Romano S, Nachum Z. The safety of quinolones in pregnancy. Obstet Gynecol Surv. 2014;69(11):681–94.
Sparks JW, Girard JR, Battaglia FC. An estimate of the caloric requirements of the human fetus. Biol Neonate. 1980;38(3–4):113–9.
Blackburn MW, Calloway DH. Energy expenditure and consumption of mature, pregnant and lactating women. J Am Diet Assoc. 1976;69(1):29–37.
Schutz Y, Lechtig A, Bradfield RB. Energy expenditures and food intakes of lactating women in Guatemala. Am J Clin Nutr. 1980;33(4):892–902.
Barks JD, Liu Y, Shangguan Y, Djuric Z, Ren J, Silverstein FS. Maternal high-fat diet influences outcomes after neonatal hypoxic-ischemic brain injury in rodents. J Cereb Blood Flow Metab. 2016.
Chu DM, Antony KM, Ma J, Prince AL, Showalter L, Moller M, Aagaard KM. The early infant gut microbiome varies in association with a maternal high-fat diet. Genome Med. 2016;8(1):77.
Saad AF, Dickerson J, Kechichian TB, Yin H, Gamble P, Salazar A, Patrikeev I, Motamedi M, Saade GR, Costantine MM. High-fructose diet in pregnancy leads to fetal programming of hypertension, insulin resistance, and obesity in adult offspring. Am J Obstet Gynecol. 2016; doi:10.1016/j.ajog.2016.03.038.
Mangesi L, Zakarija-Grkovic I. Treatments for breast engorgement during lactation. Cochrane Database Syst Rev. 2016;28(6):CD006946.
Kilpatrick SJ, Abreo A, Gould J, Greene N, Main EK. Confirmed severe maternal morbidity is associated with high rate of preterm delivery. Am J Obstet Gynecol. 2016;215(2):233. doi:10.1016/j.ajog.2016.02.026.e1-7
American College of Obstetricians and Gynecologists; Society for Maternal-Fetal Medicine. ACOG obstetric care consensus no. 3: periviable birth. Obstet Gynecol. 2015;126(5):e82–94.
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We give thanks to Nechama Kaufman for patiently organizing, reorganizing, and again reorganizing the reference list with every change that we made to this manuscript.
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Sharon Einav, Ruben Bromiker, and Hen Y. Sela declare that they have no conflict of interest.
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Einav, S., Bromiker, R. & Sela, H.Y. Maternal Critical Illness. Curr Anesthesiol Rep 7, 55–66 (2017). https://doi.org/10.1007/s40140-017-0198-5
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DOI: https://doi.org/10.1007/s40140-017-0198-5