Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

O’Donnell, 2016

[individual study characteristics deduced from O’Donnell, 2016]

PS., study characteristics and results are extracted from the SR (unless stated otherwise)

SR and meta-analysis of RCTs, non-randomized comparative studies and population-based case series

Literature search up to September 2014

A: Abas, 2014

B: Erez, 1971

C: Kashifard, 2013

D: Koren, 2010

E: Neri, 2005

F: Mohammadbeigi, 2011

G: Oliveira, 2013

H: Pongrojpaw, 2007

I: Sullivan, 1996

J: Tan, 2010

K: Tan, 2009

L: Ashkenazi-Hoffnung, 2013

M: Nelson-Piercy, 2001

N: Yost, 2003

O: Safari, 1998

P: Ziaei, 2004

Q: Bondok, 2006

R: Moran, 2002

S: Naeimi Rad, 2012

T: Evans, 1993

U: Rosen, 2003

Study design: 

A: RCT

B: RCT

C: Double-blind RCT

D: Double-blind RCT

E: RCT

F: Three-arm RCT

G: Double blinded RCT

H: Double-blind RCT

I: RCT

J: Double-blind RCT

K: RCT

L: Prospective

case–controlled

observational study

M: RCT

N: RCT

O: RCT

P: RCT

Q: Prospective

double-blind study

R: Case control

S: RCT

T: Randomized crossover trial

U: Multicenter RCT

Setting and Country:

A: Full-service, state funded university

hospital, Kuala lumpur, Malaysia

B: Prenatal clinics,

Kasimpasa Naval

Hospital and Golcuk Naval Hospital, Ismit, Turkey

C: Ruhani Hospital of Babol University of Medical Sciences,

North Iran

D: Three university

medical centres:

the University of

Texas, Texas, TX,

USA; University

of Pittsburgh, Pittsburgh, PA, USA;

and Georgetown

University, Washington, DC,

USA

E: Department of

obstetrics and

gynaecology,

University of Modena and Reggio Emilia, University of Turin, Italy

F: B’esat Hospital,

Kurdistan, Iran

G: Naval Medical

Centre, San Diego, CA, USA

H: Hospital antenatal clinic, Thammasat University Hospital,

Thailand

I: Women admitted

to the University

of Mississippi Medical Centre, MS, USA

J: Gynaecology

ward, university

hospital in Kuala

Lumpur, Malaysia

K: University of

Malaya Medical

Centre, Malaysia

L: Recruitment via

BELTIS, a free call-in centre for queries regarding drug use during pregnancy and lactation, CA, USA

M: Inpatient

gynaecology wards in eight

collaborating

centres in the UK

N: Parkland Memorial Hospital, Dallas, TX, USA

O: Women’s and children’s hospital,

Los Angeles, CA, USA

P: Najmieh Hospital, Iran

Q: Intensive care unit of Ain Shams

University Maternity

Hospital, Cairo,

Egypt

R: Inpatient antenatal ward,

hospital, Newcastle upon Tyne, UK

S: Prenatalogy clinic, Rouhani Hospital, Babol University of Medical Science, Iran

T: Obstetrics clinic, University of California, CA, USA

U: Hospital clinics and physicians’ private offices, Morristown, New Jersey, NJ, USA, Eastern Virginia Medical School, Norfolk, VA, USA, University of Arizona Health Sciences Centre, Arizona, AZ, USA, and New York University School of Medicine, New York, NY, USA

Source of funding and conflicts of interest:

Not reported for individual studies. 

Inclusion criteria SR:

- Randomised controlled trials (RCTs), non-randomized comparative studies and population-based case series

- Women experiencing nausea, vomiting and/or retching in pregnancy where recruitment

to a trial took place before 20 weeks’ gestation

- All pharmacological and non-pharmacological interventions

Exclusion criteria SR:

Not meeting the inclusion criteria

73 studies included

Important patient characteristics at baseline:

N, gestation

A: n = 160, ≤ 16 weeks

B: n = 150 (I n = 100,

C n = 50); states

treatment in first

2 months of

pregnancy only

C: n = 83, gestational age in weeks 8.7 (SD 2.6) both groups

D: n = 280;
I = 9.3 ± 2.0
C = 9.3 ± 1.8

E: n = 81 (I = 43;

C = 38). Both

groups less than

12 weeks’ gestation

F: 102 (I = 34, C = 34, placebo = 34),

ginger 9.5 ± 2.02,

metoclopramide

10.03 ± 1.99,

placebo 10.32 ± 2.25

G: n=17, first trimester

H: 170 (I = 85, C = 85),
I = 10.25 (SD 2.8),

C = 9.3 (SD 3.1)

I: n = 30, (n = 15 in

each arm);
I = 11.0 (SD 2.7)
C = 10.2 (SD 3.8)

J: n = 159;

metoclopramide

9.2 ± 2.3,

promethazine

9.3 ± 2.6

K: n = 94; Gestation: I 10.5 ± 3.1,

C 9.6 ± 2.8

L: N=58

M: n = 25,

I n = 13,

C n = 12

N: n = 126, I n = 64,

C n = 62

O: n = 40, I n = 20,

C n = 20; I

gestational age in

weeks = 9.8 (SD

2.1), C gestational

age in weeks = 9.5

(SD 2.7)

P: n = 80, I n = 40,

C n = 40

Q: n = 40, I n = 20,

C n = 20;

I = 10 ± 2.68,

C = 11 ± 2.44

R: 30 pregnancies

in 25 women in

treatment group,

matched with

25 women treated

with conventional

therapy (i.v. fluids

and antiemetics),

treatment group

median age in

weeks = 9.6 (range

8.6–11.1)

S: n=80, I=40, C=40; I = 9.55 (SD=1.81)

C = 9.45 (SD=2.02)

T: n = 25

U: n= 230

Groups were probably comparable at baseline

A: 4-mg ondansetron

was diluted in 100-ml normal saline

B: Hydroxyzine hydrochloride capsules (25 mg) two times a day (a.m. and 2 p.m. for 3 weeks)

C: Ondansetron hydrochloride tablets (4 mg), three times a day for 1 week. Dose gradually reduced and discontinues: two times a day for 3 days; once a day for 4 days. Medication stopped after second week

D: Diclectin, two tablets at night, increasing up to four tablets daily as needed.

E: Twice-weekly (for 2 weeks) acupuncture with 0.3mm diameter sterile disposable steel needles (length 52 mm) to a depth of 10–30mm to points PC6, CV12 and ST36, manipulated until the patient reported the characteristic irradiating sensation, then left in situ for 20 minutes without any further manual stimulation. Patients also advised to wear an acupressure device (sea-band) at the PC6 point for 6–8 hours a day at home

F: Ginger capsules, 200 mg, three times daily for 5 days

G: One tablet of pyridoxine (25 mg) plus one tablet of

doxylamine (12.5 mg) (P + D group) every 8 hours for 5 days

H: Ginger capsules, 500 mg, twice daily for 1 week

I: i.v. hydration. Ondansetron (10 mg) given intravenously in 50 ml of compatible i.v. fluid over 30 minutes. First dose

mandatory, then as needed 8-hourly. I.v. hydration continued until patient ingesting a bland diet.

Discharged with promethazine suppositories plus dietary instructions. Seen in clinic on a weekly basis. If no change after

48 hours patient considered treatment failure and was

excluded

J: Metoclopramide (10 mg) given i.v. after randomisation,

at 8, 16 and 24 hours

K: i.v. rehydration with saline (± potassium chloride), pyridoxine two 10 mg-tablets

given plus i.v. metoclopramide

(10 mg) given three times daily plus oral thiamine (10 mg)

daily. Discharged with pyridoxine, two tablets three times daily plus oral metoclopramide and thiamine

L: Pyridoxine (50 mg) twice daily. If vomiting persisted

plus doxylamine (25 mg) at night, with two additional doses of 12.5 mg if required

M: A 1-week course of

prednisolone, 20 mg (four 5-mg tablets) orally 12-hourly, If,

following 72 hours, a woman was still vomiting or vomiting

tablets, and still dependent on i.v. fluids and electrolyte

replacement, the therapy was changed to an i.v. equivalent

[i.e. hydrocortisone

(100 mg) 12-hourly]

N: All women: i.v. rehydration with crystalloid until ketonuria cleared [first litre included

thiamine (100mg)].

Conventional treatment:

promethazine (25mg) and metoclopramide (10mg) intravenously every 6 hours for

24 hours, followed by the same regimen orally until discharge from the hospital. The women

were also randomised, I = methylprednisolone (125 mg, i.v.). This was followed by a tapering regimen of oral

prednisone (40mg for 1 day, 20mg for 3 days, 10 mg for 3 days, and 5mg for 7 days)

O: Methylprednisolone (16 mg) orally three times a day for 3 days, followed by a tapering

regimen, halving of dose every 3 days, to none during the course of 2 weeks (10 a.m.,

2 p.m., 8 p.m.). After 2 days women were discharged with their study medication. If no

improvement study allocation unblinded and patients

withdrawn from further data collection

P: Prednisolone, (5 mg) given once in the morning for 10 days

Q: 300 mg of i.v. hydrocortisone for 3 days, followed by a tapering regimen of 200 mg for 2 days, then

100 mg for another 2 days. Patients received three syringes, each every 8 hours, 10ml each, one containing

the drug diluted in normal saline and the other two containing normal saline. Nursing services recorded the

daily number of emetic episodes

R: Oral prednisolone (10 mg) 8-hourly prescribed, replacing

traditional antiemetics. If unable to tolerate tablets stabilization achieved with i.v.

hydrocortisone (50 mg)

8-hourly. Prednisolone dosage was reduced in a stepwise fashion. Typically dosage

decreased to 15 mg daily within 5 weeks, remaining between 12.5 mg and 15 mg for a further 3–8 weeks

S: Acupressure to the two symmetrical KID21 points

T: An active batterypowered SAS wrist unit was provided to participants which they were told would produce a perceptible tingling sensation in the wrist and hand when active, while the inactive unit would produce only a pressure sensation on the wrist when stimulating the median nerve. Each subject was instructed to wear the device continually for 48 hours successively

U: Nerve stimulation for 3 weeks via a ReliefBand Model WB-R (Woodside Biomedical Inc., Carlsbad, CA, USA) [a non-invasive, portable (34 g), battery-powered, watch-like acustimulation device]. A rotary dial on the device allows users to select between five intensities

A: 10-mg metoclopramide was diluted in 100-ml normal saline

B: Identical placebo capsules two times a day (a.m. and 2 p.m. for 3 weeks)

C: Metoclopramide (10 mg), three times daily following same regime

D: Identical placebo tablet: two tablets at night, increasing up to four tablets daily as needed.

E: Metoclopramide infusion (20 mg/500 ml saline for 60 minutes) at the hospital twice a week for 2 weeks plus oral supplementation with vitamin B12 complex [pyridoxine, hydroxycobalamine, 30 mg/day (Benadon®, Roche)] was prescribed at home

F: Metoclopramide capsules, 10 mg, three times daily, and placebo (200 mg flour) for 5 days

G: One tablet of ondansetron (4 mg) plus a second (placebo) tablet (O group)

H: Dimenhydrate capsules, 50 mg twice daily for 1 week

I: As I except promethazine

(50 mg) given intravenously in 50 ml of compatible i.v. fluid over 30 minutes for initial and subsequent inpatient doses

J: Promethazine (25 mg) given i.v. after randomisation

and at 8, 16 and 24 hours

K: As I group, except instead of pyridoxine two mint Tic Tac® (Ferrero UK Ltd, Greenford, UK) given

L: Metoclopramide (10 mg) 8-hourly as needed

M: A 1-week course of placebo (four 5-mg tablets) orally 12-hourly. If, following 72 hours, a woman was still vomiting or vomiting tablets, and still dependent on i.v. fluids and electrolyte replacement, the therapy was changed to an i.v. equivalent (i.e. N-Saline)

N: All women: i.v. rehydration with crystalloid until ketonuria cleared [first litre included thiamine (100 mg)].

Conventional treatment: promethazine (25 mg) and metoclopramide (10 mg) intravenously every 6 hours for 24 hours, followed by the same regimen orally until discharge from the hospital. The women were also randomised, C = i.v. placebo. This was followed by an identical tapering regimen)

O: Promethazine (25mg) orally three times a day for 2 weeks

(10 a.m., 2 p.m., 8 p.m.). After 2 days women were discharged with study medication. If no

improvement study allocation unblinded and patients

withdrawn from further data collection

P: Promethazine was administered (25 mg), three times daily for 10 days

Q: 10 mg of metoclopramide, in a 10-ml syringe diluted

in normal saline, intravenously every 8 hours for the same

7-day period

R: Retrospective case series of

25 consecutive women hospitalized for hyperemesis but judged not to require

steroid therapy

S: Acupressure to false point

T: Not applicable

U: Participants given an identical non-stimulating device

End-point of follow-up:

A: 24 hours

B: 3 weeks

C: 8 days

D: Not reported

E: 2 weeks

F: 5 days

G: 1 week

H: 1 week

I: Not reported

J: 24 hours

K: Not reported

L: 2 years

M: Not reported

N: Not reported

O: Not reported

P: Not reported

Q: Not reported

R: Not reported

S: 4 days

T: 48 hours

U: 3 weeks

For how many participants were no complete outcome data available?

Not reported

Symptom relief outcomes

A: Nausea visual numeric rating scale scores 24 hours after randomization: 1 (IQR 1-3) vs. 2 (IQR1-3)
Vomiting episodes in first 24 hours: 1 (IQR 0-2) vs. 2 (IQR 0-2.75)

B: Hydroxyzine, partial or complete relief in 82% of the patients; placebo, some effect in 22% of the patients (p < 0.01)

C: Nausea was significantly less in the ondansetron group on third and fourth days of treatment vs. metoclopramide group (p = 0.024 and p = 0.023, respectively)

Vomiting episodes in the  ondansetron group were fewer than the metoclopramide group from the second to the eighth days

Trend of change for vomiting in the

ondansetron group was lower (p = 0.045)

No difference in nausea trend

D: Greater improvement in mean score change in Diclectin group vs. placebo (PUQE score: –4.8 ± 2.7 vs. 3.9 ± 2.6; p = 0.006)

The mean area under the curve of the change in PUQE score from baseline was significantly larger with Diclectin as compared with placebo (61.5 ± 36.9 vs. 53.5 ± 37.5; p < 0.001)

E: Nausea intensity, number of cases improved (%):
(1) I first session 1 (2.3%); second session 11 (25.5%); third session 19 (44.1%);
(2) comparator first session 1 (2.3%); second session 9 (23.6%); third session 12 (31.5%)

Vomiting episodes, number of cases improved:

(1) I first session 7 (16.2%); second session 15 (34.8%); third session 24 (55.8%);

(2) comparator first session 4 (10.5%); second session 12 (31.5%); third session 14 (36.8%)

F: Trend in symptom improvement to the 5^th day in all three groups

Nausea: ginger (p = 0.003) and metoclopramide (p = 0.001) had

significantly better improvement than

placebo, but no difference between ginger and metoclopramide (p = 0.683)

Vomiting: ginger (p = 0.046) and metoclopramide (p = 0.018) had

significantly better improvement than

placebo. No difference between ginger and metoclopramide group (p = 0.718)

G: Greater mean reduction in nausea with ondansetron (56–15 mm) vs. pyridoxine plus doxylamine (27–29mm); p = 0.02

No difference in vomiting between groups (28–25mm for ondansetron vs. 10–31mm for pyridoxine plus doxylamine; p = 0.38)

H: Nausea: mean score on days 1–7 decreased in both groups. Daily score

between groups not statistically different (p > 0.05)

Vomiting episodes: on days 1–7 decreased in both groups.

Dimenhydrinate significantly more effective on days 1–2 (p < 0.05).
Days 3–7 scores similar

I: No significant difference between treatments over 5 days of treatment via p-values

J: Vomiting: metoclopramide = 1 (IQR 0–5), promethazine = 2 (IQR 0–3);  p = 0.81

Nausea at 24 hours:  metoclopramide = 2 (IQR 1–5), promethazine = 2 (IQR 1–4); p = 0.99

(Nausea scores at 8 and 16 hours also showed no significant difference)

Repeated measures analysis of variance for nausea score: p = 0.95

K: Nausea score after 2 weeks:
I median 2 (IQR 3), usual care median 2.5 (IQR 4); p = 0.69

Vomiting after 2 weeks: I mean 1.4 (SD 1.3), usual care mean 1.4 (SD 1.6); p = 0.98

L: Moderate/severe symptoms in 28/29 of treatment group (97%) vs. 18/26 in the C group (69%) (p < 0.01) at baseline

Comparison of the treatment vs. C following treatment = similar efficacy in 20/29 (69%) vs. 18/25 (72%) of women  (p = 0.65)

M: Number still vomiting at 1 week: I 5, C 7; relative risk 1.4 (95% CI 0.6 to 3.2)

Number vomiting five or more times per day: I 2, C 5; relative risk 2.5 (95% CI 0.6 to 10.5)

Reduction in vomiting score: I median 2.0 (range –1.0 to 4.0), C median 1.5 (range –3.0 to 4.0)

Nausea score improvement I = 6.5 (range 2.0–10.0), C = 4.0 (range –5.0 to 9.0), relative risk 0.10 for proportion with nausea

N: Not reported

O: Not reported

P: Severity of nausea:

Mild/moderate: first 48 hours, I = 20

(50%), C = 30 (75%); third to tenth day, I = 6 (65%), C = 25 (62.5%); seventeenth day, I = 17 (43.6%), C = 12 (30.8%)

Severe: first 48 hours, I = 20 (50%), C = 10 (25%); third to tenth day, I = 14 (35%), C = 15 (37.5%); seventeenth day, I = 22 (56.4%), C = 27 (69.2%)

For prednisolone group OR (95% CI) of nausea: during first 48 hours OR 0.33 (95% CI 0.13 to 0.86); between third and tenth days OR 1.11 (95% CI 0.14 to 2.6); seventeenth day OR 1.7 (95% CI 0.68 to 4.4)

Episodes of vomiting: first 48 hours, I

median 3 (range 1–7), C median 1 (range 0–4), p= 0.04; third to tenth day, I median 1.5 (range 1–5), C median 1 (range 0–5), p = 0.80; tenth to seventeenth day, I median 3 (range 0–6), C median 3 (range 0–5), p = 1.0

Q: Mean vomiting episodes: hydrocortisone group reduced by 40.9% on second day, 71.6% on third day, and 95.8% on seventh day. Metoclopramide group reduced by

16.5% on second day, 51.2% on third

day, and 76.6% on seventh day (p < 0.001)

R: Six women completed VAS for nausea over 1 week. Data for intensity show a clear pattern of resolution in the active group. Three comparator group women received steroids

Median number of in patient days presteroid treatment= 8 (range 4–14) and after commencement=3

(range 1–6.5)

S: Intensity of nausea at end of treatment: 4 (IQR 5-2) vs 7 (IQR 8-5)
Frequency of nausea at end of treatment: 0 (IQR 0.75-0) vs 1 (IQR 2-0)

T: Average nausea score: 2.4 vs 2.7

Improvement in nausea: 15 vs 10

U: Mean change from baseline: 6.48 (95% CI 5.31 to 7.66) vs 4.65 (95% CI 3.67 to 5.63)

Risk of bias (high, some concerns or low):

A: Low risk of bias

B: Low risk of bias

C: Low risk of bias

D: Low risk of bias

E: High risk of bias

F: High risk of bias

G: Unclear risk of bias

H: Unclear risk of bias

I: Unclear risk of bias

J: Low risk of bias

K: Some concerns

L: High risk of bias

M: Low risk of bias

N: Unclear risk of bias

O: Low risk of bias

P: Unclear risk of bias

Q: Low risk of bias

R: Not assessed

S: Low risk of bias

T: Unclear risk of bias

U: Low risk of bias

Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

Lu, 2021

[individual study characteristics deduced from Lu, 2021]

PS., study characteristics and results are extracted from the SR (unless stated otherwise)

SR and meta-analysis of RCTs

Literature search up to January 2021

A: Habek, 2004

B: Neri, 2005

C: Jin and Hu, 2014

D: Ma, 2020

E: Wang, 2008

F: Ma and Meng, 2013

G: Zhao and Qiao, 2018

H: Zhang, 2013

I: Yan, 2012

J: Xu, 2015

K: Sun and Cui, 1995

L: Yang, 2019

M: Zhong, 2017

N: Xie, 2006

O: Mao and Liang, 2009

P: Zhang, 2005

Study design: RCT

Setting and Country:

A: Croatia

B: Italy

C-P: China

Source of funding and conflicts of interest:

Source of funding not reported. Authors declare no conflicts of interest regarding the publication.

Inclusion criteria SR:

- Patients diagnosed

with HG (diagnosed by a clinician or using

any recognized diagnostic criteria), regardless of

ethnicity, country, age, and course of the disease

- Treatment group received the common forms of acupuncture solely or combined

with other treatments, regardless of acupoint selection,

treatment frequency, or course. )e control group adopted conventional symptomatic treatment, conventional medication, placebo, sham, or no treatment. The two groups could receive the same basic treatment

- The control group adopted conventional treatment, medication, placebo acupuncture, sham acupuncture, or no treatment.

- Outcomes: the effective rate, the conversion rate of urine ketone, symptom improvement rate,

serum potassium, hospital stay, pregnancy termination rate, adverse events, and recurrence

- The study type was confined to RCTs,

and the qualified articles were limited to Chinese or

English language

Exclusion criteria SR:

- Participants with serious organic diseases or medical

diseases that can induce vomiting

- The treatment group received traditional Chinese

medicine or other forms of acupuncture (such as auricular acupuncture, hydro-acupuncture and press needle). The control group was combined with

acupuncture-related therapies.

- Trials that simultaneously conducted acupuncture and acupuncture-related therapies (such as acupressure and moxibustion) in the treatment group where the mainstay of the acupuncture

could not be identified.

- Reviews, theoretical discussion, case reports, animal experiments, crossover trials, and non-RCTs

- Duplicate publications and studies with incomplete data

16 studies included

Important patient characteristics at baseline:

Age (mean ± SD or median with range)

A: 20.4 ± 4.7 vs 20.8 ± 4.1

B: not reported

C: 25.09 ± 3.42 vs 26.03 ± 3.19

D: 31.14 ± 4.06 vs 31.36 ± 4.24

E: 27 ± 3 vs 27 ± 4

F: 26.30

G: 26 ± 3 vs 26 ± 3

H: 28.58 ± 4.57 vs 28.68 ± 3.76

I: 28.09 ± 5.78 vs 28.03 ± 6.25

J: 20–35

K: 22–34

L: 31.56 ± 6.25 vs 31.42 ± 6.37

M: 28.35 ± 2.76 vs 27.93 ± 2.47

N: 27.25 ± 3.35 vs 27.46 ± 3.29

O: 28.23 ± 4.73 vs 28.63 ± 4.86

P: not reported

Gestational age (mean ± SD or median with range)

A: 7 (6–9) vs 8 (7–12)

B: not reported

C: 9.03 ± 2.15 vs 8.98 ± 2.28

D: 8.64 ± 1.22 vs 8.36 ± 1.31

E: not reported

F: not reported

G:8.33 ± 1.94 vs 8.03 ± 1.63

H: 8.90 ± 1.66 vs 8.97 ± 1.58

I: 9.08 ± 2.44 vs 8.95 ± 2.58

J: 4–12

K: not reported

L: 8.52 ± 3.62 vs 8.86 ± 3.57

M: not reported

N: not reported

O: 8.30 ± 1.60 vs 8.33 ± 1.58

P: not reported

Groups were probably comparable at baseline

Describe intervention:

A: AP

B: AP + acupressure

C: AP + symptomatic rehydration support treatment

D: AP + symptomatic rehydration support treatment

E: AP

F: AP + TNA

G: AP + acupoint sticking

H: AP + symptomatic rehydration support treatment + psychological counseling

I: AP + symptomatic rehydration support treatment

J: AP + moxibustion + symptomatic rehydration support treatment

K: AP + symptomatic rehydration support treatment

L: AP + symptomatic rehydration support treatment

M: AP + symptomatic rehydration support treatment

N: AP + symptomatic rehydration support treatment

O: AP + symptomatic rehydration support treatment

P: AP + moxibustion

Describe  control:

A: placebo acupuncture

B: metoclopramide infusion + oral vitamin B12 complex 30 mg/day

C: symptomatic rehydration support treatment

D: symptomatic rehydration support treatment

E: symptomatic rehydration support treatment

F: TNA

G: symptomatic rehydration support treatment

H: symptomatic rehydration support treatment

I: symptomatic rehydration support treatment

J: symptomatic rehydration support treatment

K: symptomatic rehydration support treatment

L: symptomatic rehydration support treatment

M: symptomatic rehydration support treatment

N: symptomatic rehydration support treatment

O: symptomatic rehydration support treatment + oral luminal 30 mg, tid

P: symptomatic rehydration support treatment + oral luminal 30 mg, tid

End-point of follow-up:

A: over 7 days

B: 14 days

C: lasted for 5 days

D: lasted for 7 days

E: lasted for 6 days

F: lasted for 5 days

G: lasted for up to 7 days

H: lasted for 7 days

I: 3.12 ± 0.25 days/

6.32 ± 0.12 days

J: unknown

K: lasted for 3 days

L: unknown

M: unknown

N: lasted for 10 days

O: lasted for 7 days

P: 14 days

For how many participants were no complete outcome data available?

Not reported

Degree of nausea and vomiting

Effective rate

Pooled effect (fixed effects model): OR=8.11, 95%CI 5.29 to 12.43 favoring acupuncture

Heterogeneity (I²): 0%

Improvement rate of nausea intensity

B: RR=1.40, 95%CI 0.79 to 2.49

Improvement rate of vomiting episodes

B: RR=1.51, 95%CI 0.92 to 2.48

Improvement rate of nausea and vomiting

D: OR=10.48, 95%CI 0.54 to 202.47

N: OR=48.70, 95%CI 2.79 to  850.27

Hospital treatment

C: MD=-4.95, 95%CI -6.95 to
-2.95

I: MD=3.20, 95%CI -3.30 to -3.10

Inability to take in food

Pooled effect (fixed effects model): RR=1.35, 95%CI 1.01 to 1.82 favoring acupuncture

Heterogeneity (I²): 71%

Risk of bias (high, some concerns or low):

A: high

B: high

C: high

D: some concerns

E: high

F: high

G: high

H: high

I: high

J: high
K: some concerns

L: some concerns

M: some concerns

N: high

O: some concerns

P: high

Brief description of author’s conclusion

The study suggested that acupuncture was effective in treating

HG.

Limitations:

- Publication bias

- Small sample sizes

- Variation in acupuncture treatment

- Only short-term follow-up 

Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Adlan, 2017

Type of study:

Double-blind randomized controlled trial

Setting and country:

Public government hospital in Ipoh, Malaysia

Funding and conflicts of interest:

Funding not reported. No authors report any conflict of interest.

Inclusion criteria:

Women with any spontaneously

conceived singleton pregnancy between 5 and 14 weeks of gestation presenting with moderate to severe HG requiring hospital admission

Exclusion criteria:

- Women with multiple or molar pregnancy

- Patients who had prior knowledge of the acupressure band

- Presence of infections such as urinary tract infection or gastroenteritis

- Medical conditions such as hyperthyroidism

- Women with a prior history of drug reaction towards metoclopramide

N total at baseline:

Intervention: 60

Control: 60

Important prognostic factors²:

Age (mean± SD)

I: 29.0 ± 4.92

C: 28.4 ± 4.34

Gestational age (mean± SD)

I: 9.7 ± 2.09 weeks
C: 9.2 ± 2.03 weeks

Groups comparable at baseline

Describe intervention (treatment/procedure/test):

Acupressure wristband (Neiguan point) for 12 hours per day for a total of three days

Both groups: three litres intravenous fluid (1.5L of normal saline and 1.5L of Hartmann’s solution per day) and parenteral antiemetics (intravenous metoclopramide 10 mg tds)

Describe  control (treatment/procedure/test):

Normal wristband for 12 hours per day for a total of three days

Length of follow-up:

3 days

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

Degree of nausea and vomiting at three days (PUQE score)

I: 4.40 (SD=1.63)

C: 7.10 (SD=1.61)

MD=-2.70, 95%CI -3.28 to
-2.12

Hospital stay

I: 2.83 days (SD=0.62)

C: 3.88 days (SD=0.87)

MD=-1.05, 95%CI -1.32 to
-0.78

Author’s conclusion

The use of acupressure bands should be considered an adjunct or supplementary therapy to co-exist with the

standard care of management for HG, particularly in low-risk pregnant women.

Limitations

- Duration too short

- Only low-risk singleton pregnancies

Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Emami-Sahebi, 2021

Type of study:

Quasi-experimental

Setting and country:

Prenatal care clinic of Imam Referral teaching hospital in Sari, north of Iran.

Funding and conflicts of interest:

This study was supported by the Mazandaran University of Medical Sciences. The authors have no conflicts of interest relevant to this article.

Inclusion criteria:

- Women with basic literacy

- Gestational age of 6 to 12 weeks

- Singleton pregnancy

- Moderate to severe NVP determined through a score of 7 to 13 for the Pregnancy-Unique Quantification of Emesis/Nausea scale

- Women with a depression score of less than 11 for the Edinburgh Postnatal Depression Scale; and anxiety score of less than 75 for Spielberger State-Trait Anxiety Inventory

- No molar pregnancy

- No history of receiving psychotherapies in the past six months

- No affliction by gastric or duodenal ulcers

- No use of pharmaceuticals throughout the trial such as complementary therapies for NVP

Exclusion criteria:

Hospitalization and high-risk conditions (such as vaginal bleeding or the need for cervical cerclage) during the study

N total at baseline:

Intervention: 26

Control: 26

Important prognostic factors²:

Maternal age

I: 25.16 (SD=5.14)

C: 25.56 (5.79)

Gestational age

I: 8.59 (1.29) weeks
C: 8.84 (1.26) weeks

Groups comparable at baseline, except for the use of antiemetic agents

Describe intervention (treatment/procedure/test):

ICBT (six 60-minute sessions in two consecutive weeks) in addition to usual prenatal care

Sessions were held under the supervision of a psychologist by a master’s holder in midwifery who had already attended a twenty-hour CBT workshop.

During the ICBT sessions, the instructor taught participants about self-monitoring, guided imagery, stimulus control, and systematic desensitization and helped them to get actively involved in controlling the stimuli which induced or aggravated their NVP. Moreover, they were taught about coping strategies and the problem-solving and the relaxation techniques to help them acquire the ability to cope with NVP-aggravating conditions.

At the end of each session, they were given homework assignments and asked to provide feedback about them in the next session.

Describe  control (treatment/procedure/test):

Usual prenatal care

Length of follow-up:

4 weeks

Loss-to-follow-up:

Intervention: 1 (3.8%)

Due to patient not being available

Control: 1 (3.8%)

Due to the complete improvement of patient’s symptoms 

Incomplete outcome data:

Not reported

Degree of nausea and vomiting

Nausea duration

I: 1.48 hours (SD=0.77)

C: 1.72 hours (SD=0.93)

MD=-0.24, 95%CI -0.71 to 0.23

Vomiting episodes

I: 1.12 (SD=0.93)

C: 1.52 (SD=0.71)

MD=-0.40, 95%CI -0.86 to 0.06

Retching episodes

I: 1.40 (SD=0.97)

C: 1.88 (SD=0.97)

MD=-0.48, 95%CI -1.02 to 0.06

Author’s conclusion

Further investigation with a randomized control group may have some implications towards integration of psychological interventions into routine prenatal care

Limitations

- Non-random allocation

- More time was allocated to the intervention group: extra-time effort has ameliorated the symptoms  

Shakiba, 2019

Type of study:

Quasi-experimental

Setting and country:

General health centres, Iran

Funding and conflicts of interest:

Authors have no conflict of interests.

Inclusion criteria:

- Women with moderate severity of nausea

- History of HG in at least three days

- HG occurring between the 4th and the 6th week of pregnancy

- No multiple pregnancy or any other condition that would increase HCG

- No underlying medical condition in the current pregnancy

- No use of antiemetic

- No history of traumatic or distressing event during the current pregnancy

- More than 18 years of age

Exclusion criteria:

- Abortion

- No increase in the severity of nausea and vomiting and hyperemesis

- Taking drugs during the study including prescription by a physician and self-medication

- Being absent from more than one training session

N total at baseline:

Intervention: 50

Control: 50

Important prognostic factors²:

Maternal age

I: 28.58 ± 4.47

C: 29.08 ± 5.03

Gestational age

I: 22.88 ± 1.68 weeks
C: 22.16 ± 1.60 weeks

Groups were comparable at baseline except for education and gestational age.

Describe intervention (treatment/procedure/test):

Psychoeducation

Participants individually received 3 sessions (each lasting between 60 to 90 minutes) of psychoeducation based on relaxation methods for 1 week

Describe  control (treatment/procedure/test):

No additional education except for the usual pregnancy care

Length of follow-up:

4 weeks

Loss-to-follow-up:

No loss to follow-up

Incomplete outcome data:

Not reported

Degree of nausea and vomiting (PUQE)

I: 5.11 (SD=1.60)

C: 6.00 (SD=1.66)

MD=-0.89, 95%CI -1.53 to -0.25

Author’s conclusion

The psycho-education based on relaxation methods of this study had a positive and significant effect on reducing the intensity of HG. It is helpful to integrate the educational content of this intervention in the caring programs of pregnant women with nausea and vomiting.

Limitations

- Excluding highly severe forms of HG

- Not examining/comparing the time of total disappearance of HG

Truong, 2020

Type of study:

Intervention study

Setting and country:

14 community pharmacies in Norway

Funding and conflicts of interest:

None of the funding sources

had any role in the design of the study, data collection, analyses,

interpretation of data or writing the manuscript. The authors declare that they have no conflict of interest.

Inclusion criteria:

All pregnant women (≥ 18 years) in their first trimester, independent

of comorbidities

Exclusion criteria:

Not reported

N total at baseline*

Intervention: 77

Control: 75

*only women with mild/moderate NVP

Important prognostic factors²:

Not reported for women with moderate/severe NVP

Unclear if  groups were comparable at baseline.

Describe intervention (treatment/procedure/test):

Pharmacist consultation

±15 minutes consultation with information about NVP based on each woman’s needs and symptom severity according to national recommendations. Women with moderate/

severe NVP were informed about safe antiemetic

treatment. Besides, information about importance of adequate hydration was provided and women were encouraged to reach out again if NVP symptoms worsened.

Describe  control (treatment/procedure/test):

Standard antenatal care

Length of follow-up:

13 weeks after enrolment

Loss-to-follow-up:

Intervention: 20 (26%)

Control: 18 (24%)

Reason not specified for NVP subgroup

Incomplete outcome data:

Not reported

Quality of life

I: 87 (range 52 to 110)

C: 84 (38 to 105)

Author’s conclusion

The pregnant women highly appreciated the pharmacist consultation, but the intervention did

not affect their QOL scores compared with standard care.

Limitations

- Did not recruit target number of participants

- No use of NVP-specific instrument to assess quality of life

O’Donnell, 2016

Yes. Research question and inclusion criteria were clearly described.

Yes. Medline and EMBASE were searched, and search period and strategy were reported.

Yes. Reasons for the excluded studies were reported.

Yes. Characteristics were presented.

Not applicable.

Yes. Risk of bias was assessed.

Yes. Clinical and statistical heterogeneity were considered. No meta-analyses were performed because of the heterogeneity.

Yes. Authors stated that publication bias could not be assessed because of limited data. 

No. Source of funding not  indicated for the included studies.

Lu, 2021

Yes. Research question and inclusion criteria were clearly described.

Yes. EMBASE and PubMed were searched, and search period with search terms were reported. 

Yes. Reasons for the excluded studies were reported.

Yes. Characteristics were presented.

Not applicable.

Yes. Risk of bias was assessed.

Yes. Clinical and statistical heterogeneity were considered.

Yes. Publication bias was assessed with funnel plot and Egger’s test.

No. Source of funding not  indicated for each of the included studies.

Study reference

(first author, publication year)

Was the allocation sequence adequately generated?

Definitely yes

Probably yes

Probably no

Definitely no

Was the allocation adequately concealed?

Definitely yes

Probably yes

Probably no

Definitely no

Blinding: Was knowledge of the allocated

interventions adequately prevented?

Were patients blinded?

Were healthcare providers blinded?

Were data collectors blinded?

Were outcome assessors blinded?

Were data analysts blinded?

Definitely yes

Probably yes

Probably no

Definitely no

Was loss to follow-up (missing outcome data) infrequent?

Definitely yes

Probably yes

Probably no

Definitely no

Are reports of the study free of selective outcome reporting?

Definitely yes

Probably yes

Probably no

Definitely no

Was the study apparently free of other problems that could put it at a risk of bias?

Definitely yes

Probably yes

Probably no

Definitely no

Overall risk of bias

If applicable/necessary, per outcome measure

LOW

Some concerns

HIGH

Adlan, 2017

Definitely yes;

Reason: Block randomization was used. 

Probably yes;

Reason: Co-investigator applied the band according to the allocated group.

Probably yes;

Reason: Participants and investigator were blinded.

Probably yes;

Reason: No loss to follow-up reported.

Probably yes;

Reason: All relevant outcomes were reported.

Probably yes;

Reason: No other problems noted.

LOW

Study reference

(first author, publication year)

Was the allocation sequence adequately generated?

Definitely yes

Probably yes

Probably no

Definitely no

Was the allocation adequately concealed?

Definitely yes

Probably yes

Probably no

Definitely no

Blinding: Was knowledge of the allocated

interventions adequately prevented?

Were patients blinded?

Were healthcare providers blinded?

Were data collectors blinded?

Were outcome assessors blinded?

Were data analysts blinded?

Definitely yes

Probably yes

Probably no

Definitely no

Was loss to follow-up (missing outcome data) infrequent?

Definitely yes

Probably yes

Probably no

Definitely no

Are reports of the study free of selective outcome reporting?

Definitely yes

Probably yes

Probably no

Definitely no

Was the study apparently free of other problems that could put it at a risk of bias?

Definitely yes

Probably yes

Probably no

Definitely no

Overall risk of bias

If applicable/necessary, per outcome measure

LOW

Some concerns

HIGH

Emami-Sahebi, 2021

Definitely no;

Reason: No randomisation

Definitely no;

Reason: Self-selected group assignment based on their personal preferences.

Definitely no;

Reason: No blinding.  

Probably yes;

Reason: No missing data reported. 

Probably yes;

Reason: All relevant outcomes were reported.

Probably no;

Reason: Extra-time effort for intervention group has ameliorated the symptoms.

HIGH 

Shakiba, 2019

Probably yes;

Reason: Random selection by two coloured balls.

Probably not;

Reason: Participants enlisted one by one based on order of balls; no concealment.

No information

Probably yes;

Reason: No loss to follow-up reported.

Probably yes;

Reason: All relevant outcomes were reported.

Probably no;

Reason: Highly severe forms of HG were excluded.

Some concerns

Truong, 2020

Probably no;

Reason: Data pre-processing system assigned participants to one of the study groups.

No information

No information

Probably no;

Reason: Loss to follow-up was frequent but similar for both groups. 

Probably yes;

Reason: All relevant outcomes were reported.

Probably no;

Reason: Did not recruit target number of participants.

HIGH

Reference

Reason for exclusion

Abidah SN, Anggraini FD, Nisa F, Hasina SN. The Effect of Ginger Herbal Drink on Hyperemesis Gravidarum in the First Trimester Pregnant Women. Open Access Macedonian Journal of Medical Sciences. 2022;10(G):64-8.

Doubts about study quality (no randomization, risk of confounding) and does not add something to the direction of the conclusion

AlHajri L, AlFalasi M, Abdelrahim M, AlKaabi R. The efficacy of ginger for pregnancy-induced nausea and vomiting: a systematic review. Journal of Natural Remedies. 2017;17:48-56.

More recent systematic review available. No risk of bias assessment. Only 5 studies included of which 3 were included in Hu 2022

Boelig RC, Barton SJ, Saccone G, Kelly AJ, Edwards SJ, Berghella V. Interventions for treating hyperemesis gravidarum. Cochrane Database of Systematic Reviews. 2016(5).

More recent systematic review available. Only a few suitable studies

Emami-Sahebi A, Elyasi F, Yazdani-Charati J, Shahhosseini Z. Psychological interventions for nausea and vomiting of pregnancy: A systematic review. Taiwan J Obstet Gynecol. 2018 Oct;57(5):644-649. doi: 10.1016/j.tjog.2018.08.005. PMID: 30342643.

Only description of intervention and no raw data about the effects on HG

Faramarzi M, Yazdani S, Barat S. A RCT of psychotherapy in women with nausea and vomiting of pregnancy. Hum Reprod. 2015 Dec;30(12):2764-73. doi: 10.1093/humrep/dev248. Epub 2015 Oct 13. PMID: 26466913.

No women with severe NVP or HG

Grooten IJ, Koot MH, van der Post JA, Bais JM, Ris-Stalpers C, Naaktgeboren C, Bremer HA, van der Ham DP, Heidema WM, Huisjes A, Kleiverda G, Kuppens S, van Laar JO, Langenveld J, van der Made F, van Pampus MG, Papatsonis D, Pelinck MJ, Pernet PJ, van Rheenen L, Rijnders RJ, Scheepers HC, Vogelvang TE, Mol BW, Roseboom TJ, Painter RC. Early enteral tube feeding in optimizing treatment of hyperemesis gravidarum: the Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding (MOTHER) randomized controlled trial. Am J Clin Nutr. 2017 Sep;106(3):812-820. doi: 10.3945/ajcn.117.158931. Epub 2017 Aug 9. PMID: 28793989.

Reported in other module (module 7)

Hu Y, Amoah AN, Zhang H, Fu R, Qiu Y, Cao Y, Sun Y, Chen H, Liu Y, Lyu Q. Effect of ginger in the treatment of nausea and vomiting compared with vitamin B6 and placebo during pregnancy: a meta-analysis. J Matern Fetal Neonatal Med. 2022 Jan;35(1):187-196. doi: 10.1080/14767058.2020.1712714. Epub 2020 Jan 14. PMID: 31937153.

Interventions not of interest for this module or reported in other module (vitamin B6 in module 3)

Jafari-Dehkordi E, Hashem-Dabaghian F, Aliasl F, Aliasl J, Taghavi-Shirazi M, Sadeghpour O, Sohrabvand F, Minaei B, Ghods R. Comparison of quince with vitamin B6 for treatment of nausea and vomiting in pregnancy: a randomised clinical trial. J Obstet Gynaecol. 2017 Nov;37(8):1048-1052. doi: 10.1080/01443615.2017.1322046. Epub 2017 Jun 20. PMID: 28631509.

Intervention not of interest for this module or reported in other module (vitamin B6 in module 3)

Karaman E, Kaplan Ş, Alpaycı M, Çetin O, Kolusarı A, Şahin HG. Can kinesio taping be a novel treatment option for Emesis Gravidarum? A randomized preliminary study. Eastern Journal of Medicine. 2018 Jul 1;23(3):199

Intervention not of interest for this module

Matthews A, Haas DM, O'Mathúna DP, Dowswell T. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2015 Sep 8;2015(9):CD007575. doi: 10.1002/14651858.CD007575.pub4. PMID: 26348534; PMCID: PMC7196889

No interventions of interest for this module

Magfirah M, Fatma S, Idwar I. The effectiveness of acupressure therapy and aromatherapy of lemon on the ability of coping and emesis gravidarum in trimester i pregnant women at langsa city community health centre, aceh, indonesia. Open Access Macedonian Journal of Medical Sciences. 2020 Apr 25;8(E):188-92.

Doubts about study quality (emesis gravidarum, no exclusion criteria, no characteristics presented for both intervention groups, unclear how vomiting was measured)

McParlin C, O'Donnell A, Robson SC, Beyer F, Moloney E, Bryant A, Bradley J, Muirhead CR, Nelson-Piercy C, Newbury-Birch D, Norman J, Shaw C, Simpson E, Swallow B, Yates L, Vale L. Treatments for Hyperemesis Gravidarum and Nausea and Vomiting in Pregnancy: A Systematic Review. JAMA. 2016 Oct 4;316(13):1392-1401. doi: 10.1001/jama.2016.14337. PMID: 27701665.

Results were narratively synthesized without meta-analysis (same studies as O’Donnell 2016)

McParlin C, Carrick-Sen D, Steen IN, Robson SC. Hyperemesis in Pregnancy Study: a pilot randomised controlled trial of midwife-led outpatient care. Eur J Obstet Gynecol Reprod Biol. 2016 May;200:6-10. doi: 10.1016/j.ejogrb.2016.02.016. Epub 2016 Mar 2. PMID: 26963896.

Included in systematic review

Mobarakabadi SS, Shahbazzadegan S, Ozgoli G. The effect of P6 acupressure on nausea and vomiting of pregnancy: A randomized, single-blind, placebo-controlled trial. Advances in Integrative Medicine. 2020 May 1;7(2):67-72.

No women with severe NVP or HG

Negarandeh R, Eghbali M, Janani L, Dastaran F, Saatchi K. Auriculotherapy as a means of managing nausea and vomiting in pregnancy: A double-blind randomized controlled clinical trial. Complement Ther Clin Pract. 2020 Aug;40:101177. doi: 10.1016/j.ctcp.2020.101177. Epub 2020 May 4. PMID: 32891268.

No women with severe NVP or HG

Nehbandani SA, Salehi HA, Keikhaie KH, Ghalenow HR, Mirzaie FA, Badakhsh MA. The effect of ear acupressure medicine at the" Shen Men" point on the nausea and vomiting during pregnancy. Pakistan Journal of Medical & Health Sciences. 2021;15(6):1602-6.

No women with severe NVP or HG

Ozgoli G, Saei Ghare Naz M. Effects of Complementary Medicine on Nausea and Vomiting in Pregnancy: A Systematic Review. Int J Prev Med. 2018 Aug 30;9:75. doi: 10.4103/ijpvm.IJPVM_430_16. PMID: 30319738; PMCID: PMC6177529.

Only study about cardamom but did not present results. One study is suitable for cardamom but was written in Persian

Rukh L, Nazar H, Usmanghani K. Efficacy of Gingocap as compared to pyridoxine in the treatment of nausea and vomiting during pregnancy. Pak J Pharm Sci. 2016 Nov;29(6):1937-1943. PMID: 28375108.

Doubts about study quality: different data collection dates, different exclusion criteria, unclear randomization and allocation

Sharifzadeh F, Kashanian M, Koohpayehzadeh J, Rezaian F, Sheikhansari N, Eshraghi N. A comparison between the effects of ginger, pyridoxine (vitamin B6) and placebo for the treatment of the first trimester nausea and vomiting of pregnancy (NVP). J Matern Fetal Neonatal Med. 2018 Oct;31(19):2509-2514. doi: 10.1080/14767058.2017.1344965. Epub 2017 Jul 7. PMID: 28629250.

Included in systematic review

Sridharan K, Sivaramakrishnan G. Interventions for treating nausea and vomiting in pregnancy: a network meta-analysis and trial sequential analysis of randomized clinical trials. Expert Rev Clin Pharmacol. 2018 Nov;11(11):1143-1150. doi: 10.1080/17512433.2018.1530108. Epub 2018 Oct 5. PMID: 30261764.

Broader systematic review available (not specific on NVP) and difficult presentation of results because of network meta-analysis

Sridharan K, Sivaramakrishnan G. Interventions for treating hyperemesis gravidarum: a network meta-analysis of randomized clinical trials. J Matern Fetal Neonatal Med. 2020 Apr;33(8):1405-1411. doi: 10.1080/14767058.2018.1519540. Epub 2018 Sep 25. PMID: 30173590.

Broader systematic review available (not specific on HG) and difficult presentation of results because of network meta-analysis

Stokke G, Gjelsvik BL, Flaatten KT, Birkeland E, Flaatten H, Trovik J. Hyperemesis gravidarum, nutritional treatment by nasogastric tube feeding: a 10-year retrospective cohort study. Acta Obstet Gynecol Scand. 2015 Apr;94(4):359-67. doi: 10.1111/aogs.12578. Epub 2015 Feb 17. PMID: 25581215.

Reported in other module (module 7)

Van den Heuvel E, Goossens M, Vanderhaegen H, Sun HX, Buntinx F. Effect of acustimulation on nausea and vomiting and on hyperemesis in pregnancy: a systematic review of Western and Chinese literature. BMC Complement Altern Med. 2016 Jan 13;16:13. doi: 10.1186/s12906-016-0985-4. PMID: 26758211; PMCID: PMC4711053.

Specific on acustimulation; more recent systematic review available