Effect of Antenatal SSRI Exposure on the QT Interval of Neonates
Condition: Qt Interval, Variation in; Adverse Effect of Selective Serotonin Reuptake Inhibitors
Study type: Interventional

Summary: 
      Selective Serotonin Reuptake Inhibitors (SSRIs) are a group of antidepressants that suppress
      the re-absorption of a chemical called Serotonin in the brain, and improve mood. SSRI use in
      the treatment of mental health problems has increased greatly since their introduction in the
      1980's. When given in pregnancy they cause less fetal effects than other antidepressants.
      However they are still known to cause premature birth, heart defects and withdrawal symptoms
      in the baby. Withdrawal symptoms can occur in up to 30% of exposed babies, where as heart
      defects have been found to increase by 2-3 times against the normal rate of 1%. There is very
      limited information available, but it is also thought it may cause lengthening of a certain
      portion of the heart beat, the QT interval, which has been shown to lead to sudden death in
      adults. The QT interval will be looked at in this study, comparing babies exposed to SSRIs in
      pregnancy with unexposed babies.

      The study will be based in the United Kingdom (UK), at the Maternity Unit of a District
      General Hospital, and will be carried out over 12-18 months.

      A group of babies whose mothers took SSRIs whilst pregnant will have an Electrocardiogram
      (ECG) done when they are 2-3 days old. These will be compared with babies whose mothers did
      not, but whose babies were still in hospital because they were at risk of having an
      infection, but were found to be healthy.

      The study hopes to see whether there is a link between SSRI use in pregnancy and lengthening
      of the QT interval and if so, extra surveillance may be considered for this group of babies.
    

Detailed description: 
      The study will be carried out at the maternity unit of the local district general hospital.
      It is normal practice for women who have taken SSRIs in pregnancy to deliver at the local
      district general hospital, rather than at home or in the community, due to the possible
      problems with their babies.

      Currently it is standard practice for a plan of care for after the baby is born (an ALERT) to
      be generated whilst the woman is pregnant. The ALERT form is developed by specialist nurses,
      Advanced Neonatal Nurse Practitioners (ANNPs) and Doctors specialising in newborn babies. The
      ALERT form details the recommended place of birth; length of expected hospital stay; known
      side effects of SSRIs; the monitoring that is done after birth and why; and whether
      breastfeeding is advised. This is returned to community midwifery staff to discuss with the
      woman ahead of delivery. When the woman who has taken SSRIs in her pregnancy comes to the
      maternity unit to deliver the ALERT form is activated. After birth she will be assessed by
      maternity staff and ANNPs to see if her baby is suitable for the study, and if so, she will
      be given an information leaflet and invitation letter when her baby is 12 hours old by these
      staff.

      The other group of mothers that will be asked for the participation of their babies, will be
      those who require treatment with intravenous antibiotics for at least 36 hours, having been
      identified as being at risk of having an infection within 12 hours of being born. An
      infection marker, C-Reactive Protein (CRP) in their blood is measured, and if this remains
      normal after 18 hours and the baby is suitable for the study, the mother will be given an
      information leaflet and invitation letter by maternity staff/ ANNPs. Antibiotics will
      continue to be given to the baby for at least 36- 47 hours until a blood test shows whether
      they have an infection or not. If they don't have an infection and are healthy, they will be
      considered for this study.

      Both groups of babies are regularly monitored by the staff in the maternity unit to make sure
      that any problems they have are acted on quickly. Both groups of babies would normally be in
      hospital for 36- 48 hours for this monitoring.

      When the babies in both groups are 48-72 hours old, the ANNPs will ask the mother if she is
      happy for her baby to have an electrocardiogram (ECG) to look at their heart beat pattern.
      After consideration time, a consent form is signed, a data collection sheet completed, and
      the ECG is carried out on the baby. This will happen on the ward so there is minimal
      disruption to the mother and baby.

      The ECG machine used is very accurate so if it shows the heart beat pattern is normal, the
      parents are told the result and can go home. The ANNPs and Doctors specialising in the care
      of newborn babies will check the result within 24 hours.

      If the ECG machine says the heart beat pattern is not normal, then the baby remains in
      hospital, whilst the result is checked by the ANNPs and the Doctors specialising in the care
      of newborn babies, as soon as possible after it is taken. If the heart beat reading is
      abnormal, the ANNPs and Doctors specialising in the care of newborn babies will talk to the
      parents about further tests and other monitoring.

      If the confirmed ECG result is known before discharge home, the General Practitioner (GP) /
      Community staff will be told of the study and the result, on the hospital discharge letter
      the mother takes home for them. If the family have gone home before this happens they will
      receive a confirmed normal result in the post. The confirmed result will also be added to the
      electronic hospital records.

      In order to give statistically significant results, the study will be carried out over 12 -18
      months, and involve 121 babies in each group. After 50 babies have had an ECG, the results
      will be reviewed to see what results are being seen and to see if the study is following the
      original plan/ time frame.

      A statistician helped to determine how many babies would be needed for the study to show a
      difference between the two groups. However even if the difference is less than expected, the
      study may still point to the possibility of an association and provide useful data for future
      studies.
    

Intervention name(s): Electrocardiogram
Intervention type(s): Procedure
Intervention description(s): The ECG is a non-invasive screening tool. It will be performed when the neonate is settled and comfortable. The electrodes used are made with soft jelly adhesive which is stored at room temperature. The procedure will be conducted in a timely manner, taking no longer than 15 minutes. The electrodes are easily removed, and the neonate redressed.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Screening