The FILL Trial (Fluid in Low Risk Labour)
The FILL Trial (Fluid in Low Risk Labour)
The Effect of Conservative Versus Routine Intrapartum Fluid Management for Women with Epidural Analgesia on Newborn Weight Loss in Breastfed Infants
Background
Intravenous (IV) therapy during labour is a widespread practice, lacking in evidence. Fluid overload is a risk related to intrapartum IV therapy that may lead to maternal morbidity and mortality. It is also recognized that intrapartum fluid overload affects the newborn as evidenced by exaggerated weight loss in the fluid overloaded infant. The International Lactation Consultants’ Association has identified a newborn weight loss of greater than 7% as a sign of ineffective breastfeeding requiring follow up. Newborn weight loss may decrease mothers’ confidence and commitment, lead to the introduction of supplements, increase the length of stay postpartum and lead to women’s decisions to quit breastfeeding.
Women usually begin labor in a positive fluid state. There is no evidence to support current liberal intrapartum practices and some evidence from surgical trials regarding improved outcomes with conservative fluid management. The links between fluid administered to the mother, epidural analgesia administration and weight loss have been reported. A trial to evaluate the effect of a conservative intrapartum fluid management protocol on newborn outcomes is needed.
Research questions
For low risk women in labour, what is the effect of a conservative protocol for fluid management versus routine care on breastfed newborns’ weight loss prior to discharge?
For low risk women in labour, what is the effect of a conservative protocol for fluid management versus routine care on: supplementation with artificial baby milk, breastfeeding clinic visits and incidence of delayed discharge?
For low risk women in labour, what is the effect of a conservative protocol for fluid management versus routine care on: cord blood NT-proBNP, cord pH value < 7.25, admission to the neonatal intensive care unit, breast pumping and alternate methods of feeding at discharge?
Design and Purpose
The ongoing study is a single site randomized controlled trial comparing a conservative protocol of fluid management, developed by an interdisciplinary committee based on the best available evidence, with routine care for low risk women in labour. The intervention begins with the initiation of intravenous therapy and ends at delivery of the baby. All data is collected prior to discharge. An evidence-based intrapartum fluid management protocol may reduce the proportion of infants who lose greater than 7% of their birth weight, promote the initiation and exclusivity of breastfeeding and reduce health care costs related to delayed discharge or clinic visits.
Sample
The proportion of infants, born to low risk women who received epidural analgesia and planned to breastfeed, that lose greater than 7 percent of their birth weight is 28% based on a report generated by the hospital’s perinatal database summarizing births from 2004 to 2006. Sample size for this trial is based on the ability to detect a reduction from 28 to 20 percent, in the rate of infants who lose greater than 7% of their birth weight in the conservative management group. The total required sample size for a two-sided 5 percent level test of hypothesis with 80 percent power is 184 women, or 92 women per arm.
Target Population/Setting
The target population includes low risk women presenting to the Early Labour Assessment Area who are not dehydrated, who are wishing epidural analgesia and who are planning to breastfeed.
This trial is being conducted in a labour and delivery unit of a regional perinatal centre where 3,800 women give birth annually.
Data Analysis Plan
An intention to treat analysis will be used. Demographic and baseline variables will be analyzed and compared using descriptive statistics. Dichotomous variables, such as the primary outcome of weight loss greater than 7%, will be analyzed using Chi square tests. Continuous variables, such as NT-proBNP levels will be analyzed using unpaired 2-sample t tests. A p value of < 0.05 will be considered statistically significant for the primary analysis.
Measures to enhance rigor
Measures to enhance internal validity include the elimination of selection bias through the use of a web based randomization service. The use of study nurses (approximately half of the nurses were given education to provide the intervention, other nurses provide usual care) contributes to elimination of performance bias by ensuring that only women randomized to the treatment group receive the intervention. Data for the primary outcome of weight loss is collected by individuals blinded to the woman’s assignment, minimizing detection bias. External validity is enhanced since selection criteria are broad, focused on low risk women intending to breastfeed and wishing an epidural. The appropriateness of the control intervention is strengthened by the thorough development of an evidence based guideline by the transdisciplinary committee.
What new knowledge will be created?
This project will impact the availability of evidence regarding what is known about managing intravenous fluid administration in low risk labour. A systematic review has been conducted and will be submitted for publication shortly. A clinical practice guideline has been developed and implemented for evaluation in the study site. It is expected that this guideline will also be published and will guide intrapartum care for Nursing, Anesthetists and Obstetricians. This project stands to improve the safety of fluid administration in labour for women and their babies and ensure that the way Nurses provide intrapartum care is evidence based.
How did a transdisciplinary approach improve the understanding of your subject?
The transdisciplinarity of this project began with the development of a clinical practice guideline for fluid management in low risk labour. A maternal fetal medicine specialist, a generalist obstetrician, an anesthetist, a staff nurse and a nephrologist all participated in the development of the guideline. This approach ensured that all potential stakeholders would have input into the guideline and would be supportive of implementing trial results into practice.
The implementation of the trial has involved staff nurses in Labour and Delivery and Post Partum as well as anesthetists and obstetricians and family doctors. The evaluation of fluid management practices need to involve practitioners from several disciplines. All involved disciplines were represented in the conceptualization and implementation of this project.
What challenges remain?
Remaining challenges include completing the trial and the analysis and preparing manuscripts for publication to begin the process of knowledge transfer.
How will knowledge transfer take place to the concerned communities?
I planned to engage in knowledge transfer through presentations at rounds and departmental meetings at the centre where the study took place, at the university and at conferences for obstetrical care providers and lactation consultants. I also plan to submit the systematic review and the study findings for publication. Trial results could also be included in the clinical content for obstetrical placements at the University of Toronto, Faculty of Nursing
Questions for discussion
1. With a plan to present findings at obstetrical and breastfeeding conferences and to publish related findings, what more creative approaches for dissemination would you suggest?
2. Concerning IV fluid management in labour, what other outcome measures would you have considered and why?
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Hi Jo, Very interesting and
Hi Jo,
Very interesting and involved study. It's too bad there are no results available yet as I am curious to know the outcome.
In terms of thoughts about your study, a few things come to mind:
1) Are you monitoring your results as you go and will you discontinue the trial if you find one group is doing significantly better than the other group?
2) What is the difference between the conservative protocol and TAU. Are they quite different?
3) I think your topic is really cool and patients would probably be very interested in your study. Is there any way to dissemnate your results to them? Perhaps via pamphlets or posters in the waiting room, or in parenting or prenatal materials/magazines.
4) In terms of other outcome measures, this is not my area of expertise but one thing that came to mind was patient perceptions of different fluid regimens. It may not be overly relevant in this area, but I wonder if women on different regimens feel differently and if this has an impact on breastfeeding, etc.
I'm curious to hear your thoughts on this.
Alex.
Jo Watson RN, MScN,
Jo Watson RN, MScN, ACNP
Director, Obstetrics and Gynaecology
Sunnybrook Health Sciences Centre
Hi Alex
Thanks for your thoughtful questions.
Here are my responses:
1. There is no interim analysis planned and I am not monitoring results as I go. There is a safety monitoring mechanism to ensure that the intervention is safe and other than that step-reviewing any cases of adverse outcomes, there is no peeking before the recruitment is completed. Knowing interim results could bias future recruitment and data collection.
2. Regarding the difference between Usual and Conservative care
Usual Intrapartum Fluid Management
Usual intrapartum fluid management included the initiation of intravenous therapy prior to epidural analgesia administration or when intravenous drugs need to be administered. Fluid preload for epidural analgesia initiation ranged from 500cc to 1000cc of Ringers Lactate and IV fluid is administered throughout labour for non-reassuring fetal heart rate tracings and maternal fever. Hourly infusion volumes were 125 ml per hour or greater.
Conservative Fluid Management
A conservative intrapartum fluid management protocol was administered to the Conservative Care group. This protocol assumed that care would be individualized to the labouring woman and would be reflective of the events of her labour. Women received an epidural analgesia preload of 250 to 500 ml of Ringers Lactate and the intravenous infusion continued at the hourly rate of 75 to100 ml per hour. Fluid balance calculations were conducted and recorded every four hours. Reaching critical values for fluid infused > 2500 ml prompted the nurse to review the fluid management plan with the physician responsible for the woman’s care. Maternal fever was initially treated with acetaminophen rather than fluid bolus. Decisions regarding bolus for abnormal fetal heart rate patterns were at the discretion of the caregivers.
3. There are many ways to disseminate the findings and I am interested in being as creative as possible in my plans. Your ideas are good ones for dissemination, I would include web based information as well. I would like more ideas from other STIRRHS fellows through the course of this discussion.
4. Regarding patient perceptions, there were several women who declined to participate in the trial because they, or their partner felt the intervention less fluid would be unsafe.
Jo
Hi Jo, Thanks for your
Hi Jo,
Thanks for your responses. I think web-based information is a great idea. Good luck with the study.
Alex.
Hi Jo, Thanks for your
Hi Jo,
Thanks for your presentation. I am a basic scientist, don`t know some terms in your study. Can you please provide me more information about 1) what is the conservative intrapartum fluid management, what is the routine intrapartum fluid management? 2) How do you define the low risk women in labour? 3) what does NT-proBNP stand for? What can the NT-proBNP levels tell us? Many thanks!
Best Wishes for your publications,
Mingju
Jo Watson RN, MScN,
Jo Watson RN, MScN, ACNP
Director, Obstetrics and Gynaecology
Sunnybrook Health Sciences Centre
Hi Mingju
Here is the description of the differences between the intervention (conservative care) and usual IV fluid management in labour:
Usual Intrapartum Fluid Management
Usual intrapartum fluid management included the initiation of intravenous therapy prior to epidural analgesia administration or when intravenous drugs need to be administered. Fluid preload for epidural analgesia initiation ranged from 500cc to 1000cc of Ringers Lactate and IV fluid is administered throughout labour for non-reassuring fetal heart rate tracings and maternal fever. Hourly infusion volumes were 125 ml per hour or greater.
Conservative Fluid Management
A conservative intrapartum fluid management protocol was administered to the Conservative Care group. This protocol assumed that care would be individualized to the labouring woman and would be reflective of the events of her labour. Women received an epidural analgesia preload of 250 to 500 ml of Ringers Lactate and the intravenous infusion continued at the hourly rate of 75 to100 ml per hour. Fluid balance calculations were conducted and recorded every four hours. Reaching critical values for fluid infused > 2500 ml prompted the nurse to review the fluid management plan with the physician responsible for the woman’s care. Maternal fever was initially treated with acetaminophen rather than fluid bolus. Decisions regarding bolus for abnormal fetal heart rate patterns were at the discretion of the caregivers.
What is low risk?
Low risk was defined as women who had a healthy pregnancy at “no predictable risk”, according to the Ontario Medical Association Risk Scoring Tool (Ontario Medical Association, 2007
https://www.oma.org/Forms/OntarioAntenatalRecord2005.pdf. The Ontario Antenatal record has a scoring tool used to determine levels of risk.
What is NT-proBNP?
One approach to quantifying the extent of fluid overload is through the use of serum measures. Serum Brain Natriuretic Peptide (BNP) and Atrial Natriuretic Peptide (ANP) are two such serum markers that can be measured in cord blood. ANP and BNP are hormones released from the cardiac myocytes that counteract the effects of fluid overload through their action on the adrenals, kidneys and blood vessels. Datta et al., (1991) suggested that fetal neuropeptide levels may be able to provide important information about fetal well-being. This trial will attempt to determine if NT-proBNP levels are elevated in cord blood samples of newborns whose mothers receive routine fluid management intrapartum. Cord serum levels could be useful in determining whether a conservative fluid protocol maintains normal fetal NT-proBNP levels, avoiding a fluid overload response.
Jo
Hi Jo, Thank you for your
Hi Jo,
Thank you for your presentation. I've found it to be very original and interesting, especially since it could have direct impacts on patient care/mdedical practice. Here's a few question that came to mind reading your presentation.
1) Could you please describe in more detail the treatment recieved by your two groups (conservative protocol and routine care)? Do both groups recieve IV therapy (in which case what constiture the difference: volume, type of fluid, etc.)?
2) What could be the nature of a greater loss in BW (or of a greater proportion of higher BW loss) in babies that recieved IV intrapartum? Is it related to higher difficulties in breastfeeding for their mothers (volume, quality, etc.) or is it related to physiological impacts of the intrapartum IV therapy on the babies (independant of putative effects on the mothers)?
Thanks
Eric
Jo Watson RN, MScN,
Jo Watson RN, MScN, ACNP
Director, Obstetrics and Gynaecology
Sunnybrook Health Sciences Centre
Hi Eric
I have described the intervention and usual care in my responses to Alex and Mingu. All women in the trial would have had intravenous therapy since they all had decided to have epidurals.
The model explaining greater weight loss in newborns whose mothers received higher volumes of fluid relates to the process of overloading the labouring woman and some of that IV fluid would also be shared with the fetus. The newborn is then born with an artificially elevated birth weight and diureses in the first 1-2 days after birth, losing more weight than a baby that didn't have addtional fluid to begin with. I have included the conceptual model for the trial below:
Conceptual Model for the FILL Trial
Usual IV fluid in labour Conservative Fluid
Unrestricted IV during labour Conservative IV
↓ ↓
Maternal intravascular Maternal intravascular
Compartment expanded compartment not expanded
↓ ↓
Fetal Intravascular Fetal intravascular
Compartment expands does not expand
↓ ↓
Fetal fluid overload No fetal fluid overload
↓ ↓
BNP levels rise BNP levels normal
↓ ↓
Naturiesis No excess fluid loss
↓ ↓
↑ newborn weight loss Normal newborn weight loss
I hope the explanations are helpful.
Jo
Hi Jo, Thanks for the
Hi Jo,
Thanks for the presentation. As a basic scientist I learned quite a bit. I still have a few questions for you.
1. Why is IV fluid required with an epidural? Can a woman request not to have an IV?
2. How long before the epidural do IV's typically get started in the UIF group/normal birth?
3. How long after delivery is the IV usually terminated in the UIF group?
4. In the CF group why was acetaminophen used for maternal fever before the epidural? What is put in the IV normally to combat the fever? Why didn't you use acetaminophen for maternal fever later in labor for the CF group to lower their fluid volume?
5. Why was 2500ml fluid infused used at the "magic number" for review over a patients care in the CF group? What were the options for treatment upon review? For the UIF group what is the total volume of fluid infused on average?
6. How do other types of analgesia compare to epidural in their association to birthweight loss?
7. Do you know if the regular treatment for low risk women in labor is the same across Canada or are there regional differences?
8. I am a bit worried about your knowledge transfer ideas. The ideas you have stated seem very limited to dissemination to Ontario. I think it is good to start with getting the information to the physicians in your own center but if this is information that can help the health care system as a whole big picture transfer needs to be thought of. There are many doctors around Canada who are unable to go to conferences. Many babies are born in small town facilities to family doctors. Why limit yourself to the clinical content for placements at the U of T? Do you think after your trial it would be of benefit to take what you have learned and get another trial started at a facility in a different province?
Heather