Association of Non alcoholic fatty liver disease (NAFLD) and adverse pregnancy outcomes

Study type
Protocol
Date of Approval
Study reference ID
24_004113
Lay Summary

Non-alcoholic fatty liver disease (NAFLD) is a condition where extra fat builds up in the liver even if a person doesn't drink much alcohol. It is quite common, affecting about one in four people around the world. The number of cases is increasing because more people are becoming obese. In the UK, about 20-30% of adults have NAFLD, and it's also common among women who can have children.

NAFLD is particularly important to monitor during pregnancy because it can impact the health of both the mother and the baby. Research shows that pregnant women with NAFLD are more likely to develop diabetes, high blood pressure, and have babies who are born prematurely or smaller than usual. Studies have found that women with NAFLD are more likely to have these issues compared to women without NAFLD. This indicates that NAFLD can significantly affect pregnancy and needs careful management.

However, there is still much we don't know about NAFLD and its effects on pregnancy. Many studies have been small and may not represent everyone. We don't fully understand why NAFLD causes these problems during pregnancy or if different amounts of liver fat have different effects.This study aims to answer these questions by examining a large and diverse group of pregnant women. The goal is to improve health outcomes for both mothers and their babies by finding better ways to manage NAFLD during pregnancy.

Technical Summary

Aims: The aim of this study is to investigate association of the presence of NAFLD at the start of pregnancy and adverse pregnancy outcomes.
Study will be divided into three parts.
Study 1- Using the CPRD Pregnancy Register, cohort of pregnancies will be established.. Will estimate the prevalence of NAFLD among pregnancies within the CPRD Pregnancy Register. Then compare the incidence of pregnancy complications in pregnancies with and without pre-existing NAFLD. Both NAFLD and pregnancy complications will be ascertained by diagnostic codes
Study 2-Using linked HES data, cohort of delivery records will be ascertained based on OPCS and ICD10 delivery codes. We will compare the incidence of obstetric complications in pregnancies with and without pre-pregnancy NAFLD. Obstetric complications will be ascertained by both primary care and linked HES records.
Study 3-Using mother-baby linked data, cohort of babies born and linked to mothers within the CPRD Pregnancy Register will be established. We will estimate the risk of offspring outcomes between pregnancies with and without pre-pregnancy NAFLD.
A matrix of odds ratio will be tabulated quantifying the association between NAFLD and pregnancy outcomes. Based on a series of logistic regression models and will be adjusted for relevant covariates.
Exposures: coded diagnosis of NAFLD
Participants: Women aged 15 to 49 years at the start of pregnancy
Covariates: Pregnant women’s age, social deprivation, ethnicity, body mass index, smoking status, parity/gravidity, calendar year, and comorbidities will be considered as covariates for the studies.
Intended public health benefits:
With the increase in the prevalence of NAFLD in women it becomes pertinent to study the association with pregnancy.This study will ascertain potential association of NAFLD with pregnancy complications/adverse pregnancy outcomes and will help clinicians to develop appropriate strategies or suitable healthcare pathways to avoid the occurrence of these outcomes.

Health Outcomes to be Measured

Outcomes to be Measured

1-Pregnancy complications (first trimester, second trimester mainly)
1. Miscarriage
2. Hyperemesis gravidarum
3. Ectopic pregnancy
4. Hypertensive disorders of Pregnancy (Gestational hypertension, Pre-eclampsia, Eclampsia, HELLP)
5. Gestational diabetes mellitus
6.Antenatal anxiety
7.Antenatal depression
8.Postpartum anxiety
9. Post-partum depression
10.Puerperal psychosis

Study 2-Obstetric outcomes
1. Obstetric haemorrhage (postpartum)
2. Mode of Birth Caesarean delivery (HES), Instrumental
3. Perineal trauma-3rd and 4th degree
4. Stillbirth
5. Placental abruption
6. Pre-term birth
7. Small/Large for gestational age

Study 3-Adverse offspring outcomes
1. Major congenital abnormalities
2. Neurodevelopmental disorders

Collaborators

Krishnarajah Nirantharakumar - Chief Investigator - University of Birmingham
Megha Singh - Corresponding Applicant - University of Birmingham
Jingya Wang - Collaborator - University of Birmingham
Katherine Phillips - Collaborator - University of Birmingham
Krishna Gokhale - Collaborator - University of Birmingham
Steven Wambua - Collaborator - University of Birmingham

Linkages

HES Admitted Patient Care;Patient Level Index of Multiple Deprivation;CPRD Aurum Mother-Baby Link;CPRD Aurum Pregnancy Register