今日の臨床サポート

妊娠悪阻

著者: 永田愛 長崎大学 産婦人科

監修: 金山尚裕 静岡医療科学専門大学校

著者校正/監修レビュー済:2021/07/21
参考ガイドライン:
  1. 日本産科婦人科学会日本産婦人科医会:産婦人科診療ガイドライン産科編2020
患者向け説明資料

概要・推奨   

  1. 休養を心がけるよう勧め、少量頻回の食事摂取と水分補給を促す(推奨度1)。
  1. 脱水に対して十分な輸液を行う(推奨度1)。
  1. 輸液にはビタミンB1(チアミン)を添加して、Wernicke脳症を予防する(推奨度1)。
  1. ビタミンB6(ピリドキシン)投与を考慮する(推奨度2)。
  1. 閲覧にはご契約が必要となります。閲覧にはご
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要と
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
永田愛 : 未申告[2021年]
監修:金山尚裕 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行った(大幅な変更なし)。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 妊娠5~6週前後からみられる初期の悪心・嘔吐・嗜好の変化などの症状を総称して「つわり」といい、全妊婦の約80%(50%:悪心+嘔吐、25%:悪心のみ、25%:無症状)[1][2]に認められる妊娠初期の一般的な症状である。
  1. 妊娠悪阻は、つわりの重症型である。両者に明確な線引きはないが、ほぼ毎日嘔吐し、尿中ケトン体陽性で、持続的に体重が減少する場合、特に5%以上の体重減少を認める場合に、妊娠悪阻と診断する[3]
 
つわりと妊娠悪阻の主な違い

つわりと妊娠悪阻を区別する明確な基準はない。ここに示すポイントや、本人の重症感、治療の希望などを総合して判断する。悪化すると治療が難しくなるため、本人の意向も聞きながらできるだけ早い段階での介入が望ましい。

 
  1. つわりの病因については妊娠10週頃をピークとして絨毛から分泌されるhCGが関与しているとする説、免疫反応であるとする説などがあるが、いまだ明らかになっていない。
 
妊娠悪阻の病態像

つわりの原因については、妊娠10週頃をピークとして絨毛から分泌されるhCGが関与しているとする説、免疫反応であるとする説などがあるが、いまだ明らかになっていない。病状が進行すると、電解質異常や酸塩基平衡の異常を来す。また、ビタミンB1欠乏によるWernicke脳症の予後は、発症から治療開始までの期間が短いほど良好とされ、治療が遅れるほど健忘症状を主体とするKorsakoff症候群へ移行する可能性が高くなる。

出典

 
  1. 経産婦より初産婦に多い。また、妊娠年齢が低い、絨毛量が多い(胞状奇胎や双胎妊娠など)、遺伝的素因、悪阻の既往、多産、女児を妊娠[4]、ヘリコバクター・ピロリ感染[5]はリスクファクターといわれている。
  1. 悪心・嘔吐は早朝の空腹時に多くみられ、唾液の分泌亢進や嗜好の変化、全身倦怠感を訴えるものも少なくない。また、脱水による皮膚の乾燥や、動悸、乏尿、不眠などがみられることもある。
  1. 妊娠7~12週をピークとして、症状の多くは一過性であり、妊娠12~16週までに自然に消失するが、20~30%の妊婦は妊娠20週以降、まれに分娩まで症状の遷延を認める[1][6]
  1. つわりが重症化して妊娠悪阻と診断され、入院加療を要する妊婦は全体の1~2%であるが、妊娠悪阻の約10%は妊娠全期間にわたり症状が遷延する。
  1. 病状が進行すると、電解質や酸塩基平衡の異常を来し、肝機能・腎機能障害、意識障害にまで至る場合がある。
  1. ビタミンB1欠乏によるWernicke脳症を生じると、神経学的後遺症を残すこともあるため、このような状態になる前に治療を開始する。
問診・診察のポイント  
  1. 嘔気の程度や1日の嘔吐回数、食事摂取状況を確認する。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
常時アップデートされており、最新のエビデンスを各分野のエキスパートが豊富な図表や処方・検査例を交えて分かりやすく解説。日常臨床で遭遇するほぼ全ての症状・疾患から薬剤・検査情報まで瞬時に検索可能です。

まずは15日間無料トライアル
本サイトの知的財産権は全てエルゼビアまたはコンテンツのライセンサーに帰属します。私的利用及び別途規定されている場合を除き、本サイトの利用はいかなる許諾を与えるものでもありません。 本サイト、そのコンテンツ、製品およびサービスのご利用は、お客様ご自身の責任において行ってください。本サイトの利用に基づくいかなる損害についても、エルゼビアは一切の責任及び賠償義務を負いません。 また、本サイトの利用を以て、本サイト利用者は、本サイトの利用に基づき第三者に生じるいかなる損害についても、エルゼビアを免責することに合意したことになります。  本サイトを利用される医学・医療提供者は、独自の臨床的判断を行使するべきです。本サイト利用者の判断においてリスクを正当なものとして受け入れる用意がない限り、コンテンツにおいて提案されている検査または処置がなされるべきではありません。 医学の急速な進歩に鑑み、エルゼビアは、本サイト利用者が診断方法および投与量について、独自に検証を行うことを推奨いたします。

文献 

著者: R Gadsby, A M Barnie-Adshead, C Jagger
雑誌名: Br J Gen Pract. 1993 Jun;43(371):245-8.
Abstract/Text The symptoms of nausea and vomiting in pregnancy were described by 363 pregnant women who kept daily symptom diaries. All delivered a single live baby. The majority of information collected was prospective, with the median day from last menstrual period to initial interview by the study midwife being day 57. It was found that 80% of women had symptoms, 28% experienced nausea only, while 52% had nausea and vomiting. The mean number of days from last menstrual period to onset and cessation of symptoms was 39 and 84, respectively, and 40% of women's symptoms ended abruptly. Cessation of symptoms occurred at approximately the same day from the last menstrual period whether they had begun early or later, severely or mildly [corrected]. The median total number of hours of nausea per pregnancy in those 292 women experiencing symptoms was 56, with peak symptoms occurring in the ninth week. Eighty five per cent of women experienced days with two episodes of nausea. Fifty three per cent of episodes of vomiting occurred between 06.00 hours and 12.00 hours. The symptom complex can be defined as episodic daytime pregnancy sickness. Among the study population, 206 women were in paid employment. Seventy three of these women (35%) spent a mean of 62 hours away from their paid work because of symptoms of nausea and vomiting, showing the socioeconomic significance of this condition. The detailed information gathered should help in the investigation of the aetiology of nausea and vomiting during pregnancy.

PMID 8373648  Br J Gen Pract. 1993 Jun;43(371):245-8.
著者: I D Vellacott, E J Cooke, C E James
雑誌名: Int J Gynaecol Obstet. 1988 Aug;27(1):57-62.
Abstract/Text To study the problem of nausea and vomiting in early pregnancy an epidemiological survey was undertaken, obtaining information from 500 consecutive antenatal patients. Seventy-six percent of women complained of symptoms during the first trimester, and in only 27% had the symptoms resolved by the twelfth week. Job efficiency was markedly impaired. Women who suffered nausea premenstrually, or on the oral contraceptive pill, were much more likely to develop symptoms, lending credence to a hormonal etiology for the condition.

PMID 2905299  Int J Gynaecol Obstet. 1988 Aug;27(1):57-62.
著者: T M Goodwin, M Montoro, J H Mestman
雑誌名: Am J Obstet Gynecol. 1992 Sep;167(3):648-52.
Abstract/Text OBJECTIVES: Our objectives were to describe the presentation and course of hyperemesis gravidarum with respect to thyroid function and to test the hypothesis that patients with biochemical hyperthyroidism differ in clinical presentation from euthyroid hyperemesis patients.
STUDY DESIGN: Sixty-seven patients seen at Los Angeles County Women's Hospital over a 10-month period with hyperemesis gravidarum were studied prospectively with respect to thyroid function.
RESULTS: Forty-four patients (66%) had biochemical hyperthyroidism (increased free thyroxine index [n = 39] or suppressed thyroid-stimulating hormone [n = 40]) that was self-limited, resolving by 18 weeks' gestation. Hyperthyroid patients were more likely than euthyroid patients to have abnormal electrolyte levels (23/39 [59%] vs 6/28 [21%] and increased liver enzyme levels (23/59 [59%] vs 5/28 [18%], p less than 0.01). The severity of hyperemesis was found to vary directly with the degree of hyperthyroidism.
CONCLUSIONS: Hyperthyroidism is a common, self-limited finding in hyperemesis. The cause of the hyperthyroidism may be linked to the cause of hyperemesis itself.

PMID 1382389  Am J Obstet Gynecol. 1992 Sep;167(3):648-52.
著者: O Basso, J Olsen
雑誌名: Epidemiology. 2001 Nov;12(6):747-9.
Abstract/Text We examined twinning and fetal gender in births of women with a hospital diagnosis of pre-eclampsia or hyperemesis. We also investigated sex ratio in infants whose mothers had had hyperemesis or pre-eclampsia in a different pregnancy. From all the hospitalized cases in Denmark between 1980 and 1996 we extracted 6,227 births with hyperemesis and 24,764 with pre-eclampsia. Twins were more frequent in pregnancies with either condition. The male to female sex ratio was 1.04 (95%CI = 1.02-1.05) in the reference population, 0.87 (95% CI = 0.82-0.91) in births with hyperemesis, and 1.10 (95% CI = 1.07-1.12) in births with pre-eclampsia. Women with pre-eclampsia had slightly more males also in non-affected pregnancies.

PMID 11679806  Epidemiology. 2001 Nov;12(6):747-9.
著者: Irene Sandven, Michael Abdelnoor, Britt-Ingjerd Nesheim, Kjetil K Melby
雑誌名: Acta Obstet Gynecol Scand. 2009;88(11):1190-200. doi: 10.3109/00016340903284927.
Abstract/Text OBJECTIVE: To summarize the evidence from epidemiological studies examining the association between Helicobacter pylori infection and hyperemesis gravidarum.
DESIGN: Systematic review and meta-analysis of case-control studies.
MATERIAL AND METHODS: We searched the Medline/PubMed, Embase, Cinahl, ISI Web of Science and Biological Abstracts databases from 1966 to 17 June 2008 and finally Google Scholar. A total of 25 case-control studies were identified. Both fixed-effect and random-effect models were used to synthesize the results of individual studies. The Cochran Q, tau(2) of between-study variance and index of heterogeneity (I(2)) were used to evaluate heterogeneity. Heterogeneity between studies was examined by subgroup and random effect meta-regression analyses. Publication bias was evaluated.
RESULTS: Publication bias was not observed. The random model pooled estimate was odds ratio = 3.32, 95 % confidence interval (CI): 2.25-4.90. A high heterogeneity was pinpointed (I(2) = 80 %, 95 % CI: 65-89). Subgroup analysis and meta-regression showed a weaker association in studies with a clear definition of hyperemesis gravidarum compared to studies without this condition, and weaker association in recent studies compared to earlier studies. Meta-regression showed that these two study characteristics explained 40% of heterogeneity between studies.
CONCLUSIONS: Exposure to H. pylori appears to be associated with an increased risk of hyperemesis gravidarum. The residual heterogeneity might have different reasons. Given the high prevalence of H. pylori, the public health consequence of H. pylori with regard to hyperemesis gravidarum may be important.

PMID 19900137  Acta Obstet Gynecol Scand. 2009;88(11):1190-200. doi: 1・・・
著者: Glenda Linseth, Patty Vari
雑誌名: Health Care Women Int. 2005 May;26(5):372-86. doi: 10.1080/07399330590933926.
Abstract/Text Nausea and vomiting in late pregnancy is a little-studied phenomenon. In this study of 116 midwestern women, 32% of the women had nausea and vomiting after 20 weeks gestation. The purpose of this study was to examine demographic, anthropometric, maternal health factors, and pregnancy outcomes in women who had late nausea and vomiting in pregnancy (NVP) and those that did not. Women who experienced late NVP had significantly higher parity, were older, gained less weight in pregnancy, and slept fewer hours per night than women who did not experience late NVP. By being aware of prenatal factors that may affect nausea and vomiting in late pregnancy, health care providers will be better able to maximize the quality of life for these women.

PMID 16020004  Health Care Women Int. 2005 May;26(5):372-86. doi: 10.1・・・
著者: Cheryl L Attard, Michele A Kohli, Suzanne Coleman, Cathy Bradley, Margaret Hux, Gordana Atanackovic, George W Torrance
雑誌名: Am J Obstet Gynecol. 2002 May;186(5 Suppl Understanding):S220-7.
Abstract/Text OBJECTIVE: Our purpose was to determine the extent to which nausea and vomiting of pregnancy affects a woman's quality of life (QOL), ability to function, and health care resource use.
STUDY DESIGN: We conducted an observational, multicenter, prospective cohort study by gathering data on the symptoms, QOL, and health care resource use from women who have nausea and vomiting of pregnancy.
RESULTS: All 8 domains of health measured by the Short Form-36 QOL survey were limited by patient symptoms. This limitation manifested itself as patient-time loss from work and other normal activities, unpaid caregiver-time loss from work, and use of health care resources (eg, hospitalization). All types of time loss were correlated to severity of symptoms.
CONCLUSIONS: Nausea and vomiting of pregnancy can severely reduce a woman's QOL and ability to function. The degree of limitation is associated with the severity of symptoms.

PMID 12011890  Am J Obstet Gynecol. 2002 May;186(5 Suppl Understanding・・・
著者:
雑誌名: Obstet Gynecol. 2015 Sep;126(3):e12-24. doi: 10.1097/AOG.0000000000001048.
Abstract/Text Nausea and vomiting of pregnancy is a common condition that affects the health of the pregnant woman and her fetus. It can diminish the woman's quality of life and also significantly contributes to health care costs and time lost from work (). Because "morning sickness" is common in early pregnancy, the presence of nausea and vomiting of pregnancy may be minimized by obstetricians, other obstetric providers, and pregnant women and, thus, undertreated (). Furthermore, some women do not seek treatment because of concerns about safety of medications (). Once nausea and vomiting of pregnancy progresses, it can become more difficult to control symptoms; treatment in the early stages may prevent more serious complications, including hospitalization (). Mild cases of nausea and vomiting of pregnancy may be resolved with lifestyle and dietary changes, and safe and effective treatments are available for more severe cases. The woman's perception of the severity of her symptoms plays a critical role in the decision of whether, when, and how to treat nausea and vomiting of pregnancy. In addition, nausea and vomiting of pregnancy should be distinguished from nausea and vomiting related to other causes. The purpose of this document is to review the best available evidence about the diagnosis and management of nausea and vomiting of pregnancy.

PMID 26287788  Obstet Gynecol. 2015 Sep;126(3):e12-24. doi: 10.1097/AO・・・
著者: M M Weigel, R M Weigel
雑誌名: Br J Obstet Gynaecol. 1989 Nov;96(11):1304-11.
Abstract/Text The association of nausea and vomiting in pregnancy with the outcome of pregnancy was investigated in a historical cohort of 903 women in Los Angeles, California, USA. Multivariable statistical methods were employed to control for the potential confounding effects of age, ethnicity, occupation, and anti-emetic use on pregnancy outcome. The analyses indicated that vomiting was associated with decreased risk of miscarriage (adjusted odds ratio 0.18, 95% CI 0.06 to 0.53); women with nausea but no vomiting had a miscarriage risk equal to that in the sample overall. Among the subsample of women with signs of threatened miscarriage, those who had experienced vomiting had a decreased risk of miscarriage (10.3% vs 31.7% in the subsample). No statistically significant association was observed between nausea and vomiting of pregnancy and other pregnancy outcomes (perinatal mortality, fetal anomalies, neonatal anthropometric measures).

PMID 2611169  Br J Obstet Gynaecol. 1989 Nov;96(11):1304-11.
著者: J M Brandes
雑誌名: Obstet Gynecol. 1967 Sep;30(3):427-31.
Abstract/Text
PMID 6037702  Obstet Gynecol. 1967 Sep;30(3):427-31.
著者: F D Tierson, C L Olsen, E B Hook
雑誌名: Am J Obstet Gynecol. 1986 Nov;155(5):1017-22.
Abstract/Text The pattern of nausea and/or vomiting of pregnancy were investigated in a group of 414 predominantly white, upper middle-class women in Albany, New York; patterns were ascertained before their eighty-eighth day of gestation and followed up to the end of pregnancy. Of these, 89.4% reported at least some symptoms. This frequency is higher than reported previously, perhaps in part because extensive attempts were made in this study to ascertain symptoms. The incidence of vomiting was about 55%. Women with no symptoms of nausea and/or vomiting of pregnancy experienced a significantly greater proportion of nonviable pregnancy outcomes (fetal death). Increased intake of niacin during the first trimester was associated with decreased infant birth weight. This may be the result of quicker fetal maturation due to increased levels of protein intake.

PMID 3777043  Am J Obstet Gynecol. 1986 Nov;155(5):1017-22.
著者: R K Chin, T T Lao
雑誌名: Eur J Obstet Gynecol Reprod Biol. 1988 Jul;28(3):179-83.
Abstract/Text A group of patients suffering from severe hyperemesis gravidarum is defined. In contrast to what is reported in the literature, these women gave birth to babies with lower birth weight when compared to the hospital population and also to women who had a milder degree of hyperemesis gravidarum. This indicates that the metabolic disturbance created by hyperemesis may have an adverse effect on the growth potential of the fetus.

PMID 3208964  Eur J Obstet Gynecol Reprod Biol. 1988 Jul;28(3):179-83・・・
著者: S Gross, C Librach, A Cecutti
雑誌名: Am J Obstet Gynecol. 1989 Apr;160(4):906-9.
Abstract/Text Over a 5-year period in our center 64 patients were hospitalized with a diagnosis of hyperemesis gravidarum. Patients were classified into two groups to determine whether weight loss was an objective predictor of pregnancy outcome. Patients whose weight loss was greater than 5% of their prepregnancy weight were classified as group A (n = 30). Patients with nausea and vomiting of pregnancy but with maintenance of at least 95% of prepregnancy body weight were in group B (n = 34). Infants in group A were significantly smaller with respect to average birth weight expressed as a percentile for gestational age: 38.11 percentile, versus 72.00 percentile for group B (p less than 0.025). Macrosomia (greater than or equal to 4000 gm) was significantly associated with group B (18% versus group A, 0%; p less than 0.025). Growth retardation (less than or equal to 10th percentile weight at birth) was significantly associated with group A (30% versus group B, 6%; p less than 0.01). Three integumentary system abnormalities (3 of 30 cases) occurred in group A compared with none in group B. Although hyperemesis gravidarum has been viewed as a positive predictor, those patients who also demonstrate weight loss and electrolyte disturbance may be a distinct entity and at greater risk for growth retardation and fetal anomalies.

PMID 2712122  Am J Obstet Gynecol. 1989 Apr;160(4):906-9.
著者: B Källén
雑誌名: Eur J Obstet Gynecol Reprod Biol. 1987 Dec;26(4):291-302.
Abstract/Text Delivery outcome was studied in 3068 pregnancies with the diagnosis of hyperemesis in the Swedish Medical Birth Registry for the years 1973-1981. This diagnosis was present in a little over 3 per thousand deliveries in the registry but its prevalence varied enormously between different hospitals, from over 1% to practically nil. The diagnosis was over-represented at low maternal age and first parity and when the infant was a girl. Twinning occurred at a significantly increased rate. Gestational length was somewhat shorter and birthweight was lower than expected but this had no effect on perinatal survival. Congenital malformations were present slightly more often than expected and this was due to three diagnoses: undescended testicles, hip dysplasia, and Down syndrome. Possible explanations for this excess are discussed.

PMID 3691940  Eur J Obstet Gynecol Reprod Biol. 1987 Dec;26(4):291-30・・・
著者: Heleen M Koudijs, Ary I Savitri, Joyce L Browne, Dwirani Amelia, Mohammad Baharuddin, Diederick E Grobbee, Cuno S P M Uiterwaal
雑誌名: BMC Pregnancy Childbirth. 2016 Nov 25;16(1):374. doi: 10.1186/s12884-016-1174-7. Epub 2016 Nov 25.
Abstract/Text BACKGROUND: Evidence about the consequence of hyperemesis gravidarum (HG) on pregnancy outcomes is still inconclusive. In this study, we evaluated if occurrence of hyperemesis gravidarum is associated with placental dysfunction disorders and neonatal outcomes.
METHODS: A prospective cohort study was conducted in a maternal and child health primary care referral center, Budi Kemuliaan Hospital and its branch, in Jakarta, Indonesia. 2252 pregnant women visiting the hospital for regular antenatal care visits from July 2012 until October 2014 were included at their first clinic visit. For women without, with mild and with severe hyperemesis, placental dysfunction disorders (gestational hypertension, preeclampsia (PE), stillbirth, miscarriage), neonatal outcomes (birth weight, small for gestational age (SGA), low birth weight (LBW), Apgar score at 5 min, gestational age at delivery) and placental outcomes (placental weight and placental-weight-to-birth-weight ratio (PW/BW ratio)) were studied.
RESULTS: Compared to newborns of women without hyperemesis, newborns of women with severe hyperemesis had a 172 g lower birth weight in adjusted analysis (95%CI -333.26; -10.18; p = 0.04). There were no statistically significant effects on placental dysfunction disorders or other neonatal outcome measures.
CONCLUSIONS: The results of our study suggest that hyperemesis gravidarum does not seem to induce placental dysfunction disorders, but does, if severe lead to lower birth weight.

PMID 27884114  BMC Pregnancy Childbirth. 2016 Nov 25;16(1):374. doi: 1・・・
著者: Robert Brent
雑誌名: Am J Obstet Gynecol. 2002 May;186(5 Suppl Understanding):S262-6.
Abstract/Text This article will deal with medical, social, and legal implications of treating nausea and vomiting of pregnancy (NVP). Clinical problems occur when the symptoms become exaggerated and result in debilitation, dehydration, and hospitalization. The treatment of NVP in its early stages has the implication that it will prevent the more serious complications, including hospitalization. Therapeutic modalities discussed in this conference that have been used or are being tested are primarily symptomatic treatments (antihistamines, Bendectin (Merrell Dow; Cincinatti, Ohio), phenothiazines, hypnosis, accupressure, relaxation behavioral modification, audiogenic feedback training, newer medications, diet, and nutritional support). Bendectin is probably the most studied medication with regard to its reproductive effects, and the studies clearly demonstrate that therapeutic doses of Bendectin have no measurable reproductive risks to the mother or the fetus. In spite of Bendectin's record of safety, numerous nonmeritorious congenital malformation lawsuits were filed and went to trial, and that junk science was presented at these trials. The Bendectin era focused our attention on the area of nonmeritorious litigation and junk science, which could have an effect on any new or less well-studied therapies, because such a high percentage of women are treated for NVP. Because 3% of the offspring will be affected with birth defects, the potential for litigation is immense. The solutions are (1) for legal problems, the medical community should focus their attention on junk scientists and their junk science, over which physicians should have some authority, and (2) for the treatment problem, it would seem most logical that a major research effort should be directed toward brain receptors that are involved in these physiologic effects. Furthermore, it would be imperative to study the array of molecules, both natural and manufactured, that can interact with these receptors for the amelioration of nausea. Until we understand the mechanism and specific therapy for NVP, it would appear that the reintroduction of Bendectin is the logical intermediate course to follow. We should also accompany the introduction of Bendectin with an educational campaign with regard to the lack of reproductive risks for this medication. The Food and Drug Administration has set the stage for the reintroduction of Bendectin by republishing their conclusion that Bendectin does not represent an increase in reproductive risks to the fetuses of pregnant women.

PMID 12011898  Am J Obstet Gynecol. 2002 May;186(5 Suppl Understanding・・・
著者: T Vutyavanich, S Wongtra-ngan, R Ruangsri
雑誌名: Am J Obstet Gynecol. 1995 Sep;173(3 Pt 1):881-4.
Abstract/Text OBJECTIVE: Our purpose was to determine the effectiveness of pyridoxine for nausea and vomiting of pregnancy.
STUDY DESIGN: During an 11-month period 342 women who first attended Chiang Mai University Hospital antenatal clinic at < or = 17 weeks' gestation were randomized to received either oral pyridoxine hydrochloride, 30 mg per day, or placebo in a double-blind fashion. Patients graded the severity of their nausea by a visual analog scale and recorded the number of vomiting episodes over the previous 24 hours before treatment and again during 5 consecutive days on treatment.
RESULTS: There was a significant decrease in the mean of posttherapy minus baseline nausea scores in the pyridoxine compared with that in the placebo group (t test, p = 0.0008). There was also a greater reduction in the mean number of vomiting episodes, but the differences did not reach statistical significance (p = 0.0552).
CONCLUSION: Pyridoxine is effective in relieving the severity of nausea in early pregnancy.

PMID 7573262  Am J Obstet Gynecol. 1995 Sep;173(3 Pt 1):881-4.
著者: F E Franke, W Schachenmayr, M Osborn, M Altmannsberger
雑誌名: Am J Pathol. 1991 Jul;139(1):67-79.
Abstract/Text Immunoreactivities of 35 different monoclonal antibodies (MAbs) that detect intermediate filaments were studied systematically on serial cryostat sections of 14 well-defined human gliomas (five astrocytomas, three oligodendrogliomas, six glioblastomas) and on normal brain. Glial fibrillary acidic protein (GFAP), vimentin, desmin, neurofilaments, and broad-specificity keratin MAbs, as well as MAbs that recognize several or only single keratin polypeptides, were used. Unexpected reactivities were surprisingly frequent. As these may lead to diagnostic confusion and misinterpretation on this material, the authors investigated these phenomena more thoroughly. Four major sources of artifactual staining were found: 1) positive staining attributable to the rabbit gamma G immunoglobulins used in the alkaline phosphatase anti-alkaline phosphatase technique; 2) certain desmin and keratin MAbs cross-reacted with astrocytic glia and with other brain-specific epitopes; 3) technical difficulties; 4) some MAbs directed against neurofilaments and keratins showed unexpected reactivities only on individual anaplastic gliomas. The implications of these findings for intermediate filament typing of neuropathologic material are discussed.

PMID 1713022  Am J Pathol. 1991 Jul;139(1):67-79.
著者: A E Czeizel, I Dudas, G Fritz, A Técsöi, A Hanck, G Kunovits
雑誌名: Arch Gynecol Obstet. 1992;251(4):181-5.
Abstract/Text
PMID 1503509  Arch Gynecol Obstet. 1992;251(4):181-5.
著者: S Emelianova, P Mazzotta, A Einarson, G Koren
雑誌名: Clin Invest Med. 1999 Jun;22(3):106-10.
Abstract/Text OBJECTIVE: Although nausea and vomiting of pregnancy is the most common medical condition during pregnancy, there are many unanswered questions regarding its cause, epidemiologic features and optimal management. The objectives of this study were to ascertain the prevalence of nausea and vomiting in a sample of Canadian women, to characterize the distribution of their severity and to investigate the role of vitamin B6 deficiency in their etiology.
DESIGN: Prospective study.
SETTING: Antenatal counselling service for pregnant women.
PATIENTS: Three cohorts of women: a prospective, population-based cohort of 193 women, to estimate the rate and severity of nausea and vomiting (cohort A); a cohort of 555 women who sought advice for nausea with or without vomiting, to study the correlation between the maximal daily number of episodes of vomiting and maximal weight loss (cohort B); and a prospective cohort of 301 women who reported vomiting, to correlate vitamin supplementation with vomiting (cohort C).
INTERVENTIONS: All 3 cohorts were interviewed during the counselling session, and cohort B was followed up prospectively.
OUTCOME MEASURES: Frequency of nausea and vomiting, weight loss, maximal number of daily episodes of vomiting, rate of multivitamin supplementation.
RESULTS: Overall, 67% of the women in cohort A reported experiencing nausea or vomiting, or both; 22% reported vomiting, and 9% experienced weight loss. In cohort B there was a significant correlation between the maximal number of daily episodes of vomiting and maximal weight loss, although there was wide variation (r2 = 0.25, p < 0.001). There was a highly significant correlation between the number of daily vomiting episodes and mean weight loss (r2 = 0.99). In cohort C, vomiting was significantly associated with lack of supplementation with multivitamins before 6 weeks' gestation (p = 0.002).
CONCLUSIONS: The relation between number of daily vomiting episodes and mean weight loss may serve as a clinical tool to assess the severity of nausea and vomiting in pregnancy and the success of anti-emetics and rehydration regimens. Further study is needed to elucidate the biologic basis of the observed association between vomiting and lack of multivitamin supplementation in early pregnancy.

PMID 10410832  Clin Invest Med. 1999 Jun;22(3):106-10.
著者: D Jewell, G Young
雑誌名: Cochrane Database Syst Rev. 2003;(4):CD000145. doi: 10.1002/14651858.CD000145.
Abstract/Text BACKGROUND: Nausea and vomiting are the most common symptoms experienced in early pregnancy, with nausea affecting between 70 and 85% of women. About half of pregnant women experience vomiting.
OBJECTIVES: To assess the effects of different methods of treating nausea and vomiting in early pregnancy.
SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (December 2002) and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2002).
SELECTION CRITERIA: Randomised trials of any treatment for nausea and/or vomiting in early pregnancy.
DATA COLLECTION AND ANALYSIS: Two reviewers assessed the trial quality and extracted the data independently.
MAIN RESULTS: Twenty-eight trials met the inclusion criteria. For milder degrees of nausea and vomiting, 21 trials were included. These trials were of variable quality. Nausea treatments were: different antihistamine medications, vitamin B6 (pyridoxine), the combination tablet Debendox (Bendectin), P6 acupressure and ginger. For hyperemesis gravidarum, seven trials were identified testing treatments with oral ginger root extract, oral or injected corticosteroids or injected adrenocorticotropic hormone (ACTH), intravenous diazepam and acupuncture. Based on 12 trials, there was an overall reduction in nausea from anti-emetic medication (odds ratio 0.16, 95% confidence interval 0.08 to 0.33).
REVIEWER'S CONCLUSIONS: Anti-emetic medication appears to reduce the frequency of nausea in early pregnancy. There is some evidence of adverse effects, but there is very little information on effects on fetal outcomes from randomised controlled trials. Of newer treatments, pyridoxine (vitamin B6) appears to be more effective in reducing the severity of nausea. The results from trials of P6 acupressure are equivocal. No trials of treatments for hyperemesis gravidarum show any evidence of benefit. Evidence from observational studies suggests no evidence of teratogenicity from any of these treatments.

PMID 14583914  Cochrane Database Syst Rev. 2003;(4):CD000145. doi: 10.・・・
著者: A Seto, T Einarson, G Koren
雑誌名: Am J Perinatol. 1997 Mar;14(3):119-24. doi: 10.1055/s-2007-994110.
Abstract/Text To determine the relative risk for major malformations associated with antihistamine (H1 blockers) exposure in the first trimester of pregnancy, a literature search of all studies examining the association between antihistamines and major malformations for the period 1960 to 1991 was conducted, followed by meta-analysis. Odds ratio was calculated using the Mantel-Haenszel method. Twenty-four controlled studies met the inclusion criteria with more than 200,000 participating women. The summary odds ratio of major malformations associated with antihistamines taken during the first trimester was 0.76 (95% CI: 0.60-0.94). This analysis indicates that H1 blockers used mainly for morning sickness during the first trimester do not increase the teratogenic risk in humans and may, in fact, be associated with a protective effect. More study is needed to verify the possibility that by preventing vomiting, antihistamines may ensure better metabolic conditions to the fetus and thus may reduce some birth defects. Alternatively, it is possible that pregnancies characterized by vomiting are associated with better outcome due to other reasons, such as hormonal status or placental function. Women suffering from morning sickness which is not controlled by nonpharmacological methods can safely use antihistamines.

PMID 9259911  Am J Perinatol. 1997 Mar;14(3):119-24. doi: 10.1055/s-2・・・
著者: Ilan Matok, Rafael Gorodischer, Gideon Koren, Eyal Sheiner, Arnon Wiznitzer, Amalia Levy
雑誌名: N Engl J Med. 2009 Jun 11;360(24):2528-35. doi: 10.1056/NEJMoa0807154.
Abstract/Text BACKGROUND: In various countries, metoclopramide is the antiemetic drug of choice in pregnant women, but insufficient information exists regarding its safety in pregnancy.
METHODS: We investigated the safety of metoclopramide use during the first trimester of pregnancy by linking a computerized database of medications dispensed between January 1, 1998, and March 31, 2007, to all women registered in the Clalit Health Services, southern district of Israel, with computerized databases containing maternal and infant hospital records from the district hospital during the same period. We assessed associations between the use of metoclopramide in pregnancy and adverse outcomes for the fetus, adjusting for parity, maternal age, ethnic group, presence or absence of maternal diabetes, smoking status, and presence or absence of peripartum fever.
RESULTS: There were 113,612 singleton births during the study period. A total of 81,703 of the infants (71.9%) were born to women registered in Clalit Health Services; 3458 of them (4.2%) were exposed to metoclopramide during the first trimester of pregnancy. Exposure to metoclopramide, as compared with no exposure to the drug, was not associated with significantly increased risks of major congenital malformations (5.3% and 4.9%, respectively; odds ratio, 1.04; 95% confidence interval [CI], 0.89 to 1.21), low birth weight (8.5% and 8.3%; odds ratio, 1.01; 95% CI, 0.89 to 1.14), preterm delivery (6.3% and 5.9%; odds ratio, 1.15; 95% CI, 0.99 to 1.34), or perinatal death (1.5% and 2.2%; odds ratio, 0.87; 95% CI, 0.55 to 1.38). The results were materially unchanged when therapeutic abortions of exposed and unexposed fetuses were included in the analysis.
CONCLUSIONS: In this large cohort of infants, exposure to metoclopramide in the first trimester was not associated with significantly increased risks of any of several adverse outcomes. These findings provide reassurance regarding the safety of metoclopramide for the fetus when the drug is given to women to relieve nausea and vomiting during pregnancy.

2009 Massachusetts Medical Society
PMID 19516033  N Engl J Med. 2009 Jun 11;360(24):2528-35. doi: 10.1056・・・
著者: Neda Ebrahimi, Caroline Maltepe, Adrienne Einarson
雑誌名: Int J Womens Health. 2010 Aug 4;2:241-8. Epub 2010 Aug 4.
Abstract/Text Nausea and vomiting of pregnancy (NVP) is a common medical condition in pregnancy with significant physical and psychological morbidity. Up to 90% of women will suffer from NVP symptoms in the first trimester of pregnancy with up to 2% developing hyperemesis gravidarum which is NVP at its worst, leading to hospitalization and even death in extreme cases. Optimal management of NVP begins with nonpharmacological approaches, use of ginger, acupressure, vitamin B6, and dietary adjustments. The positive impact of these noninvasive, inexpensive and safe methods has been demonstrated. Pharmacological treatments are available with varying effectiveness; however, the only drug marketed specifically for the treatment of NVP in pregnancy is Diclectin(®) (vitamin B6 and doxylamine). In addition, the 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.

PMID 21151729  Int J Womens Health. 2010 Aug 4;2:241-8. Epub 2010 Aug ・・・
著者: Laura A Magee, Paolo Mazzotta, Gideon Koren
雑誌名: Am J Obstet Gynecol. 2002 May;186(5 Suppl Understanding):S256-61.
Abstract/Text OBJECTIVE: Our goal was to review the safety and effectiveness of available antiemetics for treatment of nausea and vomiting of pregnancy.
STUDY DESIGN: We performed a quantitative and qualitative overview of observational controlled studies for drug safety in pregnancy and randomized controlled trials for drug effectiveness for nausea and vomiting in pregnancy.
RESULTS: All of the following are safe and effective for treatment of varying degrees of nausea and vomiting in pregnancy: Bendectin/Diclectin (doxylamine, pyridoxine, dicyclomine), antihistamine (H(1)) blockers, and phenothiazines; however, the magnitude of effect, particularly for phenothiazines, is in question and may differ among individual agents. Pyridoxine and vitamin B(12)are safe and may be effective. Metoclopramide, droperidol, and ondansetron may be effective, but safety data are insufficient to recommend them as first-line agents. Corticosteroids may not be as beneficial as first thought, and there may be a small teratogenic risk. The relative effectiveness of various agents is largely unknown.
CONCLUSION: Many medications, particularly H(1)-antagonists and phenothiazines, are safe and effective for treatment of varying degrees of NVP.

PMID 12011897  Am J Obstet Gynecol. 2002 May;186(5 Suppl Understanding・・・
著者: H R Safari, M J Fassett, I C Souter, O M Alsulyman, T M Goodwin
雑誌名: Am J Obstet Gynecol. 1998 Oct;179(4):921-4.
Abstract/Text OBJECTIVE: The study compared the efficacy of methylprednisolone with that of promethazine for the treatment of hyperemesis gravidarum.
STUDY DESIGN: Patients with a normal-appearing intrauterine pregnancy of < or = 16 weeks' gestation with hyperemesis gravidarum (persistent vomiting and large ketonuria despite outpatient therapy) were admitted to the hospital for continuous intravenous hydration and offered participation in the study. Patients meeting study criteria were randomly assigned to receive (from identical-appearing dispensers packaged in advance with a 2-week supply) oral methylprednisolone, 16 mg 3 times daily, or oral promethazine, 25 mg 3 times daily. After 3 days the methylprednisolone was tapered completely during the course of 2 weeks whereas the promethazine was continued without change for 2 weeks. For patients who continued to vomit after 2 days the study medication was discontinued. Patients receiving study medication at discharge continued to take the remainder of the assigned medication from the packaged pill dispensers. Patients were followed up weekly. The study outcomes, as established in advance, were (1) improvement of symptoms within 2 days of starting therapy and (2) readmission for hyperemesis within 2 weeks of starting the study.
RESULTS: Forty patients were enrolled in the course of 11 months (20 per group). There were no significant differences between the groups with respect to maternal age, gravidity, parity, gestational age at entry, number of previous admissions, or > 5% body weight loss. Three patients in the methylprednisolone group and 2 in the promethazine group failed to stop vomiting within 2 days. One patient from the promethazine group was unavailable for follow-up. No patient from the methylprednisolone group but 5 of the 17 patients receiving promethazine were readmitted for hyperemesis within 2 weeks of discharge (P = .0001). There were no adverse effects noted for either drug.
CONCLUSION: A short course of methylprednisolone is more effective than promethazine for the treatment of hyperemesis.

PMID 9790371  Am J Obstet Gynecol. 1998 Oct;179(4):921-4.
著者: L Park-Wyllie, P Mazzotta, A Pastuszak, M E Moretti, L Beique, L Hunnisett, M H Friesen, S Jacobson, S Kasapinovic, D Chang, O Diav-Citrin, D Chitayat, I Nulman, T R Einarson, G Koren
雑誌名: Teratology. 2000 Dec;62(6):385-92. doi: 10.1002/1096-9926(200012)62:6<385::AID-TERA5>3.0.CO;2-Z.
Abstract/Text BACKGROUND: Corticosteroids are first-line drugs for the treatment of a variety of conditions in women of childbearing age. Information regarding human pregnancy outcome with corticosteroids is limited.
METHODS: We collected prospectively and followed up 184 women exposed to prednisone in pregnancy and 188 pregnant women who were counseled by Motherisk for nonteratogenic exposure. The primary outcome was the rate of major birth defects. A meta-analysis of all epidemiological studies was conducted. The Mantel-Haenszel summary odds ratio was calculated for the pooled studies with 95% confidence intervals. A cumulative summary odds ratio was also calculated by combining studies in chronological order. Chi-squared for homogeneity was determined to establish the comparability of the studies.
RESULTS: In our prospective study, there was no statistical difference in the rate of major anomalies between the corticosteroid-exposed and control groups. In the meta-analysis, the Mantel-Haenszel summary odds ratio for major malformations with all cohort studies was 1.45 [95% CI 0.80, 2.60] and 3.03 [95% CI 1.08, 8. 54] when Heinonen et al. ('77) was removed. This suggests a marginally increased risk of major malformations after first-trimester exposure to corticosteroids. In addition, summary odds ratio for case-control studies examining oral clefts was significant (3.35 [95% CI 1.97, 5.69]).
CONCLUSIONS: Although prednisone does not represent a major teratogenic risk in humans at therapeutic doses, it does increase by an order of 3.4-fold the risk of oral cleft, which is consistent with the existing animal studies.

Copyright 2000 Wiley-Liss, Inc.
PMID 11091360  Teratology. 2000 Dec;62(6):385-92. doi: 10.1002/1096-99・・・

ページ上部に戻る

戻る

さらなるご利用にはご登録が必要です。

こちらよりご契約または優待日間無料トライアルお申込みをお願いします。

(※トライアルご登録は1名様につき、一度となります)


ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから