Motherisk algorithm provides a guideline for use of safe and effective drugs for the treatment of NVP. Optimal medical management of symptoms will ensure the mental and physical wellbeing of expecting mothers and their developing babies during this often stressful and difficult time period. Dismissing NVP as an inconsequential part of pregnancy can have serious ramifications for both mother and baby.
Human chorionic gonadotropin (hCG) is a glycoprotein hormone produced by the placenta, which has a similar structure to thyroid-stimulating hormone (TSH).Due to this similarity, hCG could exhibit TSH-like activity and stimulate thyroid gland to produce thyroid hormones, particularly thyroxine (T4).This condition is often seen at end of the first trimester of pregnancy (weeks 10-12). In these cases, maternal serum TSH concentration is reduced and T4 level is elevated, causing overt hyperthyroidism that could lead to thyrotoxicosis if remain untreated. Pregnant women with hyperemesisgravidarum experience nausea and vomiting. These subjects seem to have elevated levels of serum hCG, particularly at the end of the first trimester when it reaches its peak, eventually leading to hyperthyroidism. There are some reports suggesting that hyperemesis gravidarum might be due to hyperthyroidism associated with elevated hCG in pregnant women at weeks10-12 of pregnancy .
Relaxin has previously been implicated with PGP, how- ever, its role in PGP is currently inconclusive [46, 47]. Although high levels of relaxin have been suggested as contributing in the underlying mechanisms of PGP , when examining the other outcomes in our study, low levels of relaxin seem more plausible for the NVP group here. In addition to the examples mentioned, relaxin is also found to be involved in resetting the osmotic threshold for thirst and antidiuretic hormone release during early pregnancy . A low level of relaxin would thus cause a delay in resetting, accompanied by aberrant water intake patterns, elements that have been suggested in previous studies [10, 49]. By virtue of the higher placental- and birth weights observed, the NVP and NP women have most likely experienced a higher plasma Table 4 Delivery and birth outcomes in relation to group (symptom-free (SF), nausea only (NP), and nausea and vomiting (NVP))
Abstract: Nausea and vomiting in pregnancy (NVP) is common and often undertreated, in part due to fears of adverse effects of medications on the fetus during early pregnancy. In April 2013, the US Food and Drug Administration (FDA) approved doxylamine succinate 10 mg and pyridoxine hydrochloride (a vitamin B 6 analog) 10 mg as a delayed-release combination pill called Diclegis for the treatment of NVP. Diclegis is currently the only medication that is FDA-approved for the indication of NVP. This review addresses the historical context, safety, efficacy, pharmacology, and practical role of doxylamine and pyridoxine for the management of NVP. The reintroduction of this doxylamine–pyridoxine combination pill into the American market fills a therapeutic gap in the management of NVP left by the removal of the same active drugs marketed over 30 years ago in the form of Bendectin. The substantial amount of safety data accumulated over the years makes it one of the few drugs that qualify for FDA Pregnancy Category A status. In the hierarchical approach to pharmacological treatment of NVP, the combination of doxylamine and pyridoxine should thus be first-tier.
Dealing with the significance of this issue is because women with mild to moderate NVP experience suffer depression, reduced function of employment, home activity, parental roles, and other physical and social activities. NVP increases the cost and use of health care resources. In addition, in some cases, pregnant women decide to terminate their pregnancy due to the complications of these symptoms . It has been shown that preterm birth in the group with severe longing is clearly more prevalent than the patients with mild longing . The risk factors for NVP include low maternal age, first pregnancy, female embryo, and twins . In other studies, fetal abnormalities, history of nausea and vomiting in the previous pregnancy are related to mental and psychological conditions of the individuals, and the increase and decrease in BMI before pregnancy and the economic and social status associated with NVP . Overall, the most important and commonly used NVP treatments include non-pharmaceutical treatments, such as special diets and the use of medication treatments. The popularity of complementary and alternative medicine, such as non-pharmaceutical treatments and herbal extracts has grown significantly in recent years, and the prevalence of using complementary and alternative therapies during pregnancy have been significant. In Iranian traditional medicine, one of the common treatments for NVP has been the use of ginger . Ginger is an herb used in traditional medicine to treat all types of nausea and vomiting, such as NVP . The precise mechanism of ginger as an anti-nausea and vomiting agent has not been completely known. Ginger seems to control the mechanism of the transmission of serotonin messages at the gastrointestinal system  that can be due to its direct effect on the intestinal duct. Its antiemetic effect through the central nervous system is debatable because there are compounds in ginger that inhibit type 3 serotonin receptors that have not been known well .
Results: Doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg use was not associated with an increased rate of any adverse event over placebo, including CNS depression, gastrointestinal or cardiovascular involvement. Conclusions: Doxylamine succinate – pyridoxine hydrochloride delayed release combination is safe and well tolerated by pregnant women when used in the recommended dose of up to 4 tablets daily in treating nausea and vomiting of pregnancy.
the treatment of nausea and vomiting of pregnancy by women using the NVP counseling line at the Motherisk Program at the Hospital for Sick Children in Toronto, On- tario, Canada. Because the use of CAM has become more prevalent in the general population in recent years, cou- pled with the fact that 70% of all pregnant women suffer from NVP, one might be able to extrapolate these results to the general population of women who suffer from NVP, but did not call the NVP helpline. It is a fact that women who call the NVP helpline do have a higher SES status and it is known that SES status has an impact on the use CAM.(19) However, there was no correlation between the use of CAM and higher SES in our study, the only fac- tor that predicted the use of CAM was the severity of NVP. This finding may appear to be suprising, however it was not to us at the Motherisk NVP Helpline, because over the years, many women have told us that NVP can be so de- bilitating that they will try just about anything to alleviate their symptoms.
Official obstetric guidelines need to adequately emphasize the oral health issues related to nausea and vomiting in pregnancy and ways to reduce the effect. This study sug- gests that the use of a solution of a teaspoon of baking soda (sodium bicarbonate) in a cup of water for mouth rinses, one of the non-pharmacological methods of deal- ing with nausea and vomiting is not popular. The need to neutralize the acid from the vomitus is highlighted with respondents advising pregnant women to rinse with clean water only after vomiting. Tooth brushing immediately after vomiting is not recommended, how- ever resident obstetricians were giving pregnant women incorrect advice.
12-Soules MR,Hughes CL, Garsia JA,Livengood CH,Prystowsky MR, Alexander E. Nausea and vomiting of pregnancy :role of human chorionic gonadotropin and 17- hydroxyprogesterone.Obstet Gynecol. 1980 .55:696-700 . 13-Fantz CR,Dagogo-Jack s, Ladenson JH. Gronowski Thyroid Function during pregnancy.Clin chem.1999 Dec;45(12):2250-8. 14-Rashid M, Rashid MH. Obstetric management of thyroid disease. Obstet Gynecol Surv.2007;62(10):680-8
Background: Nausea and vomiting of pregnancy (NVP) affects up to 80% of expecting mothers. In April 2013 the FDA approved the delayed-release combination of doxylamine succinate and pyridoxine hydrochloride (Diclegis®) for NVP, based in part, on the results of a phase III randomized trial demonstrating the efficacy of this drug combination [study drug marketed under the trade name Diclectin® in Canada and Diclegis® in the United States] compared to placebo in pregnant women. Study drug dosing occurred for 14 days, which is substantially longer than what has been performed in similar studies. The objective of this study was to evaluate, through secondary analysis, whether the primary measure of efficacy can be demonstrated after five days of treatment.
tioning , and on stress levels . In addition, the pres- ence and severity of NVP have been shown to have an impact on the quality of life (QOL) of pregnant women [9-11]. Since health-related QOL is a non-negligible out- come when evaluating the burden of illness of health problems, it is important to have a valid way of measuring this health issue. Some generic measures of health-related QOL are available, but the only existing NVP-specific QOL questionnaire is the "Health-Related Quality of Life for Nausea and Vomiting during Pregnancy" (NVPQOL) . However, the reliability and criterion validity of the NVPQOL have never been established.
Introduction: This study aimed to assess the impact of wearing compression stockings on women’s quality of life (QoL) associated with nausea and vomiting in early pregnancy (NVP). Methods: In this randomized, open, single-center, crossover study, 74 women were assigned 1:1 to 2 weeks with compression stockings followed by 2 weeks without or vice versa. The main outcomes were NVP-associated QoL, leg-related QoL, and dizziness, as assessed by the Nausea and Vomiting in Pregnancy Quality of Life (NVPQOL) questionnaire, Chronic Venous Disease Quality of Life (CIVIQ) questionnaire, and questions on dizziness at baseline and after each 2-week period, respectively. Daily NVP was assessed using the modified Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) questionnaire. Data were analyzed using Pearson’s chi-square and independent t-tests.
This clinical trial was approved by the Ethical Research Committee of Kashan University of Medical Sciences. The participants of this study were pregnant women who were referred to the Prenatal Care Unit of Naghavi Hospital Kashan/Iran. This clinic is the only center that provides pre- natal care ten hours per day. The inclusion criterion were: 1) being a volunteer, 2) suffering from nausea and/or mild to moderate vomiting, 3) gestational age less than 16 weeks, 4) singleton pregnancy, 5) reading and writing ability, 6) no digestive disease, 7) no history of treatment with other anti-vomiting drugs within the last three weeks, and 8) resi- dency in Kashan. The exclusion criterion included: subjects who did not complete the forms, subjects that experienced side effects from consuming ginger capsules, subjects who were advised that the treatment was not effective and that they needed further treatment, and subjects who vomited more than five times per day.
Q2 included a food frequency questionnaire and was answered in mid-pregnancy. Version two of Q2 included detailed questions regarding nausea and vomiting, there- fore only women answering this version were included in the sample. While the questions regarding NVP and PGP in Q1 were structured simply as ‘yes/no’ for the corresponding 4 week intervals in early first trimester, the NVP questions in Q2 probed experiences of nausea or vomiting during pregnancy (yes or no), the gesta- tional week of onset and cessation, and whether women were still experiencing nausea and/or vomiting at the time of answering the questionnaire (around gestational week 20). These NP and NVP answers were cross- checked with answers provided in Q1 to avoid inconsist- ent responses, as detailed in the ‘Study Sample’ section below. Prior to calculating the duration of either nausea or vomiting from variables stating the gestational week of onset and the week of cessation of these conditions, recoding for some variables was required, as described in detail previously .
In regard to status migrainosus, many cases may require hospital admission to achieve an optimalmanagement. Status migrainosus refers to severe migraine episodes that last more than 72 hours, usually accompanied by severe nausea and vomiting, that can impede oral administration of drugs. In these cases, fluid replacement, correction of fluid and elec- trolyte imbalances (if present) and quitting of nausea and vomiting with intravenous metoclopramide, chlorpromazine, or prochlorperazine is needed. Neuroleptics may be useful because of their sedative and antiemetic action (eg, 100 mg of intravenous tiapride dissolved in dextrose). Administration of intravenous corticosteroids, such as 4–8 mg of dexametha- sone every 6–8 hours or 20–40 mg of prednisolone every 6–8 hours, with a subsequent tapering dose for 3–4 days, is also effective in controlling headache and the accompany- ing symptoms. Analgesics and NSAIDs have a minor role in these cases, but may be helpful as adjuvants when combined with other drugs. Nonoral formulations of triptans (such as 6 mg of subcutaneous sumatriptan, 10–20 mg of intranasal sumatriptan, or 5 mg of intranasal zolmitriptan) are the initial treatment of choice. Intravenous DHE (0.5 mg) combined with intravenous antiemetics is effective too. It can be admin- istered every 8 hours if the headache does not stop. 75
These findings are similar to the results of a Norwegian large cohort study showing higher prevalence of preterm births in women who did not experience NVP than in women who did experience NVP . Czeizel showed that women who had medically recorded NVP and were treated for it had longer gestational age and a lower pro- portion of preterm birth than women who had mild NVP without any treatment or hospitalization due to hyperem- esis gravidarum . Klebanoff reported lower rates of preterm births in women who reported vomiting during pregnancy . These two results are also similar to our findings, whereas Naumann and Weigel reported no asso- ciation between NVP and rate of preterm births [18, 19], and Temming reported higher rates of preterm births in women who reported NVP .
trimester of pregnancy. Finally, missing values are not a major concern in our study because less than 3% of differ- ent maternal characteristic variables were missing. As for external validity, we feel confident that our study population is representative of the Montreal population. The high degree of racial/ethnic diversity of our region provides a greater generalizability of our results. Moreo- ver, the majority of women in our study population were Caucasians. Consequently, it improves the external valid- ity of our results to the Canadian population. In fact, in 2001 less than 15% of the Canadian population were from a visible minority group . The high education level and the high proportion of women having a house- hold income greater than $80,000/year, which can be explained by the geographic location of the René-Laennec clinic (provided 63% of our study cohort), could however limit the external validity of our study. Finally, because we achieved more than one recruitment site, we are confident that our study cohort is representative of the population of pregnant women receiving prenatal care without an overrepresentation of high-risk pregnancies.
A recently published systematic review involving 37 trials and 5,049 women investigated interventions for the treat- ment for HG. Interventions examined included acupressure, acustimulation, acupuncture, ginger, chamomile, lemon oil, mint oil, vitamin B6, and several antiemetic drugs. Again, the review was significantly limited by heterogeneity in study participants, interventions, comparison groups, and outcomes measured or reported. Acupuncture showed no significant benefit to women in pregnancy. Ginger may have some ben- efits, but the evidence was limited. Pharmacological agents including vitamin B6 and antiemetic drugs may help relieve mild or moderate nausea and vomiting. 62 Administration of
Pregnancy is a normal physiological condition that ends at nine month with a healthy born infant. However, vulnerable pregnant women are liable to develop morning sickness, nausea and vomiting of pregnancy (NVP), hyperemesis gravidarum (HG), Wernicke’s encephalopathy (WE), Korsakoff syndrome and Wernicke- Korsakoff syndrome (WKS) during the progression of pregnancies [1,2]. HG is an emergency condition that affects 0.3-3 % of all pregnancies . NVP occurs in 50% to 90% of all gravida and its onset starts at 4-8 weeks and subsides in 90 % cases by 16-20 weeks. However, NVP may persist beyond 20 weeks in 13% of cases and may progress to HG [2-5]. HG characterized by pernicious nausea and vomiting, dehydration, electrolyte and fluid imbalance, weight loss, and ketonuria and necessitates hospital admission [2,3]. Hundreds of cases and studies have reported HG, WE, WKS and central pontine myelinolysis (CPM) in the literature with marked variability in clinical picture, laboratory findings, response to treatment and fetal, offspring and maternal outcome [5-10]. The etiology of HG is multifactorial and its pathophysiology is not yet fully understood [5-7,11]. Furthermore, HG is reported to be aggravated by diverse co- occurring systematic diseases, surgical complications, WE, KS, and WKS, and needs multimodal approach including surgical interventions [12-17]. HG a prime cause of acute thiamine deficiency if not treated effectively progresses to WE, KS, WKS and CPM. Overall, only a small proportion of vulnerable pregnant women with or without prior thiamine deficiency tend to develop aforesaid sequential syndromes  requiring emergency admission to the
The severity of these symptoms is often mild and self-limiting and usually responds to conservative treatments. Nausea and vomiting of pregnancy (NVP) is often labeled as “morning sickness”, even though up to 80% of patients encounter these symptoms throughout the day, with only 1.8% of patients experiencing these symptoms solely in the morning. Symptoms of NVP typically begin between the 4th and 7th week after the last menstruation, peak around the 9th week of gestation, and in most pregnancies, resolve around the 20th week of gestation. In a small number of patients, the symptoms persist throughout the whole pregnancy. 9