Prescribing medication provides a challenge for physicians when considering a pregnant patient. Here the beneficial effect of the drug must be balanced against possible adverse effects on the mother and unborn child. For many drugs prescribed throughout pregnancy, there is very little definitive evidence of safety as pregnant women are rarely recruited to clinical trials for ethical and practical reasons. This presents a significant problem as there are a range of chronic conditions requiring ongoing treatment, such as depression, diabetes, hypertension, and thyroid conditions that may precede or develop during the pregnancy. This use necessitates a method to safely and accurately discern whether there are adverse offspring outcomes associated with these treatments, alongside evaluating the extent of the maternal benefit. Electronic healthcare databases are a source of routinely collected, anonymised healthcare data which can be used to investigate associations between intrauterine drug exposure and maternal and neonatal outcomes, whilst avoiding the possible dangers of implementing randomised control trials. Thus, we aim to use available observational data to investigate potential risks currently associated with prescriptive drugs under circumstances where we are unable to perform a randomised controlled trial. To establish this evidence, we will investigate the relationship between maternal drug prescriptions and adverse and beneficial offspring outcomes to provide evidence to guide clinical decisions.
It is increasingly common for pregnant women to be prescribed medication for chronic conditions. Depression and antidepressant use are increasingly common in women of a child-bearing age, with studies suggesting that up to 20% of pregnant women suffer from depression during pregnancy [1]. In addition, cardiovascular related conditions are relatively common, with 15% of pregnant women experiencing hypertension. Although less common, endocrine conditions, such as diabetes and thyroid disorders, are persistent and problematic within pregnancy, affecting around 4% and 10% of pregnant women respectively [2, 3].
These conditions are well-established risk factors for numerous adverse maternal and neonatal such as preeclampsia, stroke, and preterm birth if left untreated. Yet, treatments for these conditions are associated with additional neonatal risks, with many studies finding evidence of teratogenic effects. There is also conflicting evidence surrounding potential adverse neurodevelopmental outcomes following exposure to antidepressants in utero [4]. With limited pharmacoepidemiological data to support their effects in human populations, information to make clinical recommendations during pregnancy is limited.
The aims for this study are to determine whether medication prescribed for depression, diabetes, hypertension and thyroid disordered are associated with (1) maternal risk, (2) neonatal risk and (3) offspring risk. We will address the first of these aims by conducting an observational cohort study to investigate the relationship between prescribed medications for these conditions in pregnancy with maternal outcomes. Then, we will utilise the same approach to analyse neonatal risk following use of these medications in pregnancy. Thirdly, we will address offspring risk by analysing treatment use during pregnancy to determine the effects of the drug exposures on long-term childhood outcomes. Together, these findings will enhance available knowledge of maternal prescriptive drug use, enabling more informed clinical decisions to be made in the future.
Outcomes to be measured
Maternal outcomes, depression: Incidence of depression during pregnancy; severity of depression during pregnancy
Maternal outcomes, diabetes: Gestational diabetes; episodes of hypo- or hyper-glycaemia
Maternal outcomes, hypertension: Hypertensive disorders of pregnancy
Maternal outcomes, thyroid related: Common symptoms of thyroid malfunction; episodes of thyroid malfunction
Maternal outcomes, all four conditions investigated: Mode of delivery; post-partum haemorrhage; post-partum all-cause hospitalisation
Neonatal outcomes, : stillbirth (delivery at ≥24 weeks with an Apgar score of 0,0,0); miscarriage (foetal loss <24 weeks); elective termination of pregnancy; birthweight; birthweight for gestational age; birth length; head circumference; gestational age (preterm delivery <37 weeks); impaired growth; Apgar score <7 at 1, 5, 15 minutes; congenital defects.
Childhood outcomes: autism spectrum disorder (ASD); attention deficit hyperactivity disorder (ADHD); intellectual disability (ID) in childhood.
Venexia Walker - Chief Investigator - University of Bristol
Ciarrah-Jane Barry - Corresponding Applicant - University of Bristol
Dheeraj Rai - Collaborator - University of Bristol
Florence Martin - Collaborator - University of Bristol
Gemma Sharp - Collaborator - University of Bristol
Harriet Forbes - Collaborator - University of Bristol
Karishma Krishna - Collaborator - University of Bristol
Kayleigh Easey - Collaborator - University of Bristol
Paul Madley-Dowd - Collaborator - University of Bristol
Neil Davies - Collaborator - University of Bristol
Venexia Walker - Collaborator - University of Bristol
Karishma Krishna - Collaborator - University of Bristol
CPRD Mother-Baby Link;HES Admitted Patient Care;Mental Health Services Data Set (MHSDS);ONS Death Registration Data;Practice Level Index of Multiple Deprivation;Pregnancy Register