Nausea and vomiting of pregnancy

11.1

Nausea and vomiting of pregnancy

One of the most frequently encountered common discomforts related to pregnancy is nausea and vomiting. Nausea and vomiting of pregnancy (NVP) is often most difficult to deal with, often debilitating to patients, relationships, work performance, and severely impacts quality of life (QOL) if untreated or poorly controlled. While likely multifactorial in nature, there is no “magic bullet” or formula which may be successfully applied to all women; treatments for afflicted women must be considered on an individual basis [ ], and prevention is likely the best approach [ ]. It is understood that NVP and hyperemesis gravidarum (HG) decrease absorption of many drugs resulting in diminished therapeutic concentrations, while pH changes in the stomach alter drug bioavailability [ ]. Drug distribution is further altered due to increased maternal plasma volume; a decrease in plasma protein during pregnancy may result in more unbound, metabolically active drug levels which affect drug excretion [ ].

11.2

Prevalence

Statistics vary regarding prevalence, but many authors agree NVP occurs in up to 70–91% of pregnancies [ , , ]. Authors may differentiate nausea from retching and actual vomiting and agree this debilitating process may occur anytime of the day or night [ ]. A challenge to the study of this malady is lack of consistent definitions used among researchers [ ] and data collection challenges related to inconsistencies in ICD-10 hospital coding [ ].

NVP often begins in the fourth to sixth week of pregnancy, reaching peak prevalence during weeks 8–12, and diminishing by week 20 [ , ], although approximately 10% of women continue to experience NVP throughout pregnancy [ ]. Women who experience severe and prolonged NVP are said to have HG, the most severe form of the problem. Although this extreme form of NVP occurs in only approximately 1%–3% of the pregnant population [ , , ], it is quite challenging to deal with and recurs in about 75% of subsequent pregnancies [ ].

HG is generally defined as severe, persistent, and prolonged NVP beginning before 20 weeks of pregnancy and associated with dehydration, ketonuria, and loss of ≥5% loss of body mass index (BMI), often requiring hospitalization to achieve symptom relief [ , , ]. Electrolyte disturbances and abnormalities in liver function occur in approximately 50% of HG sufferers [ ]. As the most common reason for hospitalization in the first half of pregnancy [ ], the effects of HG severely impact QOL, often result in orthostatic BP and heart rate changes, and may portend postpartum depression [ , , ]. Rarely, women with HG experience Wernicke encephalopathy, splenic avulsion, esophageal rupture, and pneumothorax [ ]; as such, it is suggested when administering IV fluids they be of lactated ringers solution with added thiamine (B-1) to prevent Wernicke encephalopathy [ ]. Because NVP is such a common occurrence, providers, family members, and employers may minimize its significance [ ], leading women to feel unsupported and labeled lazy or complainers and ultimately experiencing feelings of being dismissed and not heard by providers and family. Those who equate NVP with a protective response to preserve pregnancy may, unfortunately, undertreat patients [ ].

NVP and HG have global significance, affecting relationships with significant others, caretaking other children, and employment. Women experience emotional sequelae and economic burdens from these conditions and may ultimately consider termination of the current pregnancy and prevention of any future pregnancies [ ]. Women with severe NVP or HG experience diminished QOL as their symptom severity increases; however, even mild symptoms impact women's ability to perform in the workplace, care for their children, and maintain satisfying relationships with friends or partners [ , , ]. These women may decide to delay or decline future pregnancies and even consider termination if symptoms are severe and unrelenting [ ]. Health care professionals may dismiss symptoms as trivial [ ]; however, it is critical to intervene early to prevent development of HG [ ].

11.3

Etiologies and pathogenesis

11.4

Burden of the disease

Many authors agree NVP and HG are leading causes of hospitalization in early pregnancy [ , , ]. The economic burden of NVP was estimated at $1827 per pregnancy by Ref. [ ] and/or approximately $1.8 billion in 2012 in the United States [ , ]. Multiple unscheduled visits to care providers, telephone contacts, and utilization of ambulance or EMT services increase costs for caring for NVP and HG patients [ , ]. Diminished job effectiveness and time lost from work contribute to the economic and psychological burden women suffered [ ]. Negative experiences HG may meet criteria for posttraumatic stress disorder [ ], suggesting a relationship between degree of symptoms, hospitalization, and risk of prenatal and postpartum anxiety and depression [ ].

While the impact on QOL is more difficult to measure, most authors agree there are significant negative effects on partner and parenting relationships, job performance, and fulfillment of household responsibilities [ , ]. However, QOL studies related to NVP and HG are subject to profound recall bias complicating research [ ]. Providers must acknowledge grieving processes associated with loss of normal, uncomplicated pregnancy experiences and instead offer support to deal with disruption of QOL by significant symptoms [ ]. Heitman et al. reported while even mild NVP negatively impacted women's lives, with severe symptoms, women were less likely to consider future pregnancies. Authors agreed all modes of therapeutic management should be utilized before therapeutic abortion is considered [ ]. Evaluating length of stay per hospital admission and improved quantification of symptom severity assist approximations of current cost burden [ , ], as use of incorrect diagnosis codes may result in underreporting admissions for NVP, compounding errors in determining financial burden [ ].

11.5

Cultural implications

It is interesting to note some cultures lack words to describe NVP; as a result, diminished self-worth and self-esteem and being thought of negatively by family may result [ ]. Difficulty describing the experience of NVP and HG among pregnant women in some cultures is made more difficult by food insecurities, taboos, cultural mores, and norms. Precluding pregnant women from consuming potentially tainted foods, especially meat, milk, and vegetables, may be perceived as problematic, especially younger women with less education, subject to direction from powerful and influential family members. Women may not know or understand the basis of foods recommended or prohibited; however, adherence may be rooted in cultural and evolutionary factors [ ]. NVP occurs more commonly in women from India, Pakistan, Asian, and New Zealand compared to other populations [ ]. Some authors attribute NVP to an evolutionary mechanism resulting in better precautions around behaviors and intake and promoting additional social support [ , , ]; however, this may result in undertreatment of symptoms.

11.6

Risk factors

NVP occurs more often in women who are obese, younger, primigravidas, and nonsmokers [ ]. Other risk factors include multiple gestations, molar pregnancies and pregnancies with female infants, and factors related to an increase in hCG levels [ , ]. Younger women had a higher risk of NVP and had a two times higher likelihood of hospital admission [ ]. Smoking seems to exert a protective effect against NVP [ ], perhaps due to decreased placental size [ ] suggested lower socioeconomic status (SES) as a risk for worse NVP; others, however, found no evidence of association of SES, BMI, or smoking status with NVP [ ]. Additionally, women with a history of motion sickness or migraines may experience worse symptoms; avoiding flickering lights and high-humidity environments may be helpful preventive tactics [ , ].

11.7

Quantification

The PUQE, or Pregnancy Unique Quantification of Emesis scoring system, is a frequently employed system used to assess the severity of NVP based on the presence of nausea, vomiting, and retching during a 24-h period. It has been repeatedly validated for use [ , , ]. This three-question survey differentiates between nausea, vomiting, and retching, with a maximum of 15 points possible, helping categorize severity of NVP into “mild” (≤6 points), “moderate” (7–12 points), and “severe” (≥13 points). It also contains a QOL question with no points attached (see Fig. 11.1 ). Rhodes Index Score (see Fig. 11.2 ) is also a valid and reliable tool for self-quantification of postoperative nausea and vomiting and is also used to determine the extent of NVP [ ]. Future work includes the MinSafeStart mobile application, currently being developed in Norway, to help quantify symptoms of NVP and optimize treatment [ ].

11.8

Effects on fetus

Some authors purport no association between HG and lower APGAR scores or perinatal mortality [ ]. [ ] implies a possible but unclear connection between the severity of NVP and low birthweight (LBW), small for gestational age (SGA), and preterm births. While there are multifactorial etiologies suspected, children of women with severe NVP and HG may experience developmental disabilities such as seen with Autism Spectrum Disorder including impaired social, verbal, and nonverbal communication abilities [ ].

11.9

Late complications related to NVP

Authors suggested there was an increased risk of preeclampsia, proteinuria, and/or HTN with NVP, which appeared related to elevated hCG levels; however, there appeared to be a lower risk for LBW or SGA infants with NVP [ ], while other authors suggested that mild-to-moderate NVP was associated with improved outcomes, such as fewer miscarriages and fetal malformations, less prematurity, and better attainment of developmental milestones [ , ].

11.10

Approaches to treatment

Generally, authors agree treatment must be individualized for every patient and could relate to individual metabolic activity as well as differences in drug bioavailability [ ]; 1- [ , ]; further, authors agree that prevention and early treatment of symptoms is better than identifying which treatments are effective after symptoms arise [ , ]. It is appropriate to utilize simpler interventions, such as lifestyle changes, before employing higher level interventions such as pharmaceuticals [ ]. However, there is a dearth of evidence-based study related to effective lifestyle changes [ ] and few medication studies that included the vulnerable population of pregnant women. This results from regulatory change following the Thalidomide disaster in 1961 [ ]. While there are adverse drug events websites for reporting complications around drugs used in pregnancy, most premarketing human clinical trials exclude pregnant women, promoting reliance on less rigorous studies [ ].

Authors generally agree that avoidance of medications in the first trimester is advisable [ , ]; however [ ], studies suggest nearly half the women who were admitted for symptomatic control of NVP had not previously received a prescription medication. Clinicians following treatment guidelines may prevent initial or recurrent hospital admissions and related resource utilization [ ]. Following a logical, stepwise plan using antiemetics and additional strategies will be helpful to combat NVP and HG [ ].

11.11