Nutrient deficiency and Hyperemesis Gravidarum

• Research type

  Research Study

• Full title

  The NUTRIENT study: Nausea and vomiting in pregnancy : Implications on nutritional status and maternal-fetal outcomes

• IRAS ID

  322879

• Contact name

  Caroline Ovadia

• Contact email

  caroline.ovadia@kcl.ac.uk

• Sponsor organisation

  King's College London

• Clinicaltrials.gov Identifier

  N/A, N/A

• Duration of Study in the UK

  2 years, 3 months, 29 days

• Research summary

  Hyperemesis gravidarum (HG) is a severe form of nausea and vomiting in pregnancy. It affects around 2/100 pregnancies. Women vomit up to 60 times per day and symptoms can last throughout the whole pregnancy. Some women become so distressed that they abort a wanted pregnancy or have suicidal thoughts.

  Their babies are more likely to have problems with brain development and have increased risk of heart disease, obesity and diabetes (known as ‘metabolic diseases’) in later life. These issues may result from low levels of nutrients during the pregnancy. Only four small studies have investigated this; one measured blood nutrient levels, the others used information from food diaries to estimate nutrient intake. These studies suggested that women with HG had very low levels of many nutrients (often lower than half the recommended amount). We know that low levels of some nutrients during pregnancy are linked to brain development problems and risk of future metabolic disease in the children of women with other medical problems, but this has not been confirmed in HG.

  We aim to:
  1. Establish if essential nutrient levels are low in HG-women
  2. Determine consequences on maternal function and mental health
  3. Determine effects on the babies

  70 women with HG and 70 with uncomplicated pregnancy will be recruited. Mothers’ nutrient levels will be measured four times throughout pregnancy. They will also be asked to keep a food diary for 24-hours before the study visits (using an app) and have a functional status and mental health assessed at each visit. A blood sample from the umbilical cord and baby will be taken to measure the babies’ nutrient levels and other factors that can predict future risk of metabolic disease.

  If nutrient deficiency exists in HG and/or contributes to poor brain development and increased risk of metabolic diseases, replacement nutrient treatments could be developed in future studies.

  Purpose and design
  Hyperemesis Gravidarum (HG) is currently the leading cause of hospital admission for women in the first trimester of pregnancy. It is associated with both physical and mental health consequences and increased rates of neurodevelopmental and metabolic problems for the children. However, little is know about the mechanism by which these consequences occur. We hypothesise that they relate to nutritional deficiency, but this has not been studied. This question is a key priority for HG researchers as defined in the James Lind Alliance Priority Setting Partnership exercise. Our centre has a tertiary level UK-leading HG service and this potential to recruit patients who fit criteria and close collaborations with colleagues in Cambridge who will analyse the nutrient concentrations will allow us to ensure that the results are high quality. The study has been developed between both the obstetrics and neonatal departments at St Thomas’ Hospital to ensure maximum value is achieved. Study visits have been planned to co-incide with routine hospital appointments to minimise time burden to patients and costs for the study. The study will in part form the basis of a NIHR-funded PhD for Dr Melanie Nana (see A2-1).

  Recruitment
  Patients will be recruited from three main places with support of research midwives:
  - Patient booking visits
  - Referrals to the antenatal clinic
  - Referrals to the gynaecology unit

  Inclusion/exclusion:

  Women in the HG study group must meet ≥1 of the following criteria indicating severe-HG:
  • still having symptoms with second-line medication;
  • Pregnancy-Unique Quantification of Emesis score ≥13 on treatment;
  • weight loss ≥5 kg or ≥10% of pre-pregnancy body weight.

  The control group will include:
  • women with a singleton pregnancy matched for parity, ethnicity and body mass index (BMI) to the women with HG.

  Exclusion criteria include:
  • women with underlying chronic medical conditions and mental health conditions (may affect nutritional status);
  • women taking medications known to affect nutrient absorption.

  Consent

  The participant must personally sign and date the latest approved version of the Informed Consent Form (ICF) before any of the study specific procedures are performed.

  Written versions of the Participant Information Sheet (PIS) and Informed Consent will be presented to the participants detailing the exact nature of the study, what it will involve for the participant, the implications and constraints of the protocol and any risks involved in taking part. It will be clearly stated that the participant is free to withdraw from the study at any time for any reason without prejudice to future care, and with no obligation to give the reason for withdrawal.

  The participant will be allowed as much time as they need to consider participation in the study. They will be offered sufficient opportunities to question the Investigator, GP or other independent parties to decide whether they will participate in the study. Participants will not be rushed into making a decision. However, the convenience of the participant will also be considered, including the right to immediate consent.
  
  Written Informed Consent (consent will be obtained electronically where convenient for the participant) will then be obtained by means of participant dated signature and dated signature of the person who presented and obtained the Informed Consent. A member of the research team will go through the written information with the potential participant giving the opportunity for questions to be asked. Only researchers experienced in consent procedure and trained in Good Clinical Practice will take consent from participants.

  In gaining consent from the participant we will ensure that the participant is able to:
  1. Understand the purpose and nature of the research
  2. Understand what the research involved including potential benefits and burden
  3. Understand that the alternative to taking part is for them to receive standard medical care and that this is not affected by participation
  4. Retain information long enough to make an effective decision
  5. Make a free choice

  If there is any further safety information that may result in significant changes in the risk/benefit analysis, the PIS and Informed ICF will be reviewed and updated accordingly. All participants that are actively enrolled on the study will be informed of the updated information and given a revised copy of the PIS/ICF in order to confirm their wish to continue on the study.

• REC name

  London - Fulham Research Ethics Committee

• REC reference

  23/PR/0749

• Date of REC Opinion

  8 Aug 2023

• REC opinion

  Further Information Favourable Opinion