It has been a busy day. You finally crawl into bed listening to the sounds of the tropical storms in the distance and the air conditioner gently humming away on its never-ending battle against the humidity. You are hoping for a solid night’s sleep; however, you concur with the alleged postulation that stormy weather seemingly brings on labour. Therefore, your phone is adjusted to the highest volume next to your bed, as you fall into a gentle slumber, despite the rumbles of the passing storms.
All too soon, you are abruptly woken by the symphony of the loud thunderclap and the blaring ringtone of the phone. Half dazed, you answer and recognise the voice of the night midwife. ‘Sorry to wake you doc, but can I speak to you about a 26 weeker? She has come in contracting, about three in 10. No fluid loss or bleeding, the baby looks great on CTG, but we are definitely getting some activity with the toco. I don’t have all her history yet as she is not booked with us, but did you want me to do a spec and any swabs?’ Hearing this history, you thank him between the claps of thunder, but decide you better head in and see what is happening.
As you open the front door, hit by the humidity and the pelting rain, you start to think about the patient you are about to see. For the last three years, you have been the obstetrician in a rural country town, about twelve hours’ drive from the city. You have a great team of five GP obstetricians, two paediatricians, never enough midwives and a level two nursery that can handle babies from 35 weeks of gestation. The closest tertiary hospital is nine hours away; if, and only if, there is a plane and a pilot (who hasn’t exceeding their daily flight limit) hours within the region. As you drive in, it is the golden oldies hour on the radio and a song by The Clash grabs your attention, ‘Should I stay, or should I go.’ You chuckle as you realise it is the same question for this patient. Should she stay out bush with you or be shipped off to the big smoke? And more importantly, how will you answer that question?
Should they stay or should they go?
For patients presenting with threatened preterm labour in a rural area, often the right and safest answer appears to be simply sending them to the closest hospital with an appropriate nursery should they deliver. Research has consistently demonstrated that in utero transfers are much safer and cost-effective, compared to the increased risks and resources required to transfer a preterm neonate.1 A local paediatrician will have to accompany the preterm neonate, divesting the region of their expertise for days. The time-critical nature of the transfer mandates dispatch of the faster, but more expensive, jet.2 The possibility of mother and baby separation should also be considered, if both cannot be transported on the same plane. With all this in mind, the answer seems quite simple, you have to get her out.
But, what if she’s not actually in labour, but has a urinary tract infection, gastroenteritis or an irritable uterus? By transferring every patient with threatened preterm labour ‘just in case’, there are considerable financial and resource implications that can potentially compromise other patients in the community. Each transfer can cost up to tens of thousands of dollars3 and, even more concerning, there will be one less plane available for other local emergencies, such as an acute myocardial infarction or a cerebral vascular accident. Furthermore, once patients with threatened preterm labour are evacuated from rural areas, there is an understandable reluctance for the medical team to facilitate the patients’ return, until an appropriate gestation has been attained. This can result in patients being ‘stuck’ in metropolitan areas for weeks or months, and consequently missing work and income, as well as increasing stress from trying to coordinate family and childcare responsibilities back at home. Many rural patients describe feeling very lonely, depressed and isolated under such circumstances.4
You soon pull into the hospital carpark and brave through the warm rain to the labour ward. You know to make the right diagnosis and treatment plan for this patient, you are going to need to take into consideration her history, examination and potentially use bedside tests. You quickly run through these in your mind, and the evidence for their use.
Preterm labour is commonly defined as regular uterine contractions (greater or equal to four every 20 minutes or greater than eight per hour) with a cervical length of less than 20 mm on transvaginal ultrasound, or, positive fetal fibronectin (fFN) and a cervical length between 20–29 mm on transvaginal ultrasound, between 20 and 36+6 weeks of gestation.5 Factors to consider as part of threatened preterm labour workup are listed in Table 1.
Table 1. Factors to consider as part of workup for threatened preterm labour.
*In the absence of relative contraindications to a digital cervical examination, findings can add more clinical value to a speculum examination.
As you arrive on the labour ward, you are informed that the patient has had two previous deliveries at term. This singleton pregnancy has been uncomplicated to date and she has never had any gynaecological surgery before. With a limited on-call radiology service, you have a portable ultrasound machine in the labour ward and wonder about cervical length. You consider this in your diagnosis, and the other risk factors for preterm birth, summarised in Table 2.
Table 2. Risk factors associated with preterm birth.
You decide to examine the patient and take swabs at the same time to see if this will assist in your diagnosis. In the labour ward storeroom, there are a number of threatened preterm labour tests that companies have sent for you to try, each with literature explaining why theirs is the best. You wonder if any has an advantage over the others. A device for quantifying fFN has also been purchased recently, and you wonder if it has any advantage over the cheaper bedside test.
There are three main commercial kits available to risk-stratify patients at risk of preterm labour. Studies regarding their efficacy are often industry sponsored, with published findings in Table 3.6 7 8
Table 3. Positive and negative predictive values of bedside tests for delivery within seven days.
|Protein||Positive predictive values %||Negative predictive values %|
|Fetal Fibronectin (fFN):|
|> 10 ng/mL
> 50 ng/mL
> 200 ng/mL
> 500 ng/mL
|16.7 (95% CI 13.3–20.5)
|97.3 (95% CI 96.1–98.2)
|Placental alpha microglobulin-1 (PAMG-1)||76–78||94–96|
|Phosphorylated insulin-like growth factor binding protein-1 (pIGFBP-1)||83–86||95–98|
Often in rural areas, only one particular test kit may be available. Therefore, practitioners must ensure that they are familiar with the manufacturer’s instructions for each test, as differences exist with collection and testing. Furthermore, the test is only one of the determining factors used in in the assessment of risk of PTL, taking into account the clinical context.
Upon completion of the patient’s sonography assessment, the cervix was found to be only 10 mm in closed length. The midwife subsequently informs you that the fFN level is greater than 200 ng/mL and the patient is still experiencing mild contractions, despite attempts at tocolysis with nifedipine. Your clinical instinct tells you that transfer to a tertiary unit is warranted. You call the Royal Flying Doctor Service that provides your state medical emergency transport service. They answer, ‘Yeah doc, we can get her out, but we need to move soon as cyclone Winston is headed your way and all planes will likely soon be grounded for a couple of days. I am sure the roads will also be cut.’ As you quickly prepare the patient for evacuation and transfer, a number of thoughts cross your mind regarding transferring a patient with threatened preterm labour from a rural area.
Risk of delivery in the air
With the contractions only partially settling, you wonder about placing the patient on the plane. A preterm delivery can be difficult on its own, let alone at 20,000 feet. You wonder who should be sent on the plane.
While research has demonstrated that aeromedical transfers have not been associated with in-flight preterm delivery,9 deliveries outside hospital add further risks that must be contemplated and negated by considering the accompanying personnel; the need to carry delivery and neonatal resuscitation supplies and even cross-matched blood. Patients in active labour, at high risk of bleeding or with fetal distress, should not be considered for transfer except in extreme circumstances.
With the delivery potentially occurring in the next few hours or days, you wonder about the benefits of steroid administration for acceleration of fetal lung maturation.
While it is well established that optimal timing for antenatal corticosteroid administration, to prevent respiratory distress syndrome (RDS), to delivery is between 48 hours and one week,10 less evidence is known about the effects if delivery occurs within 24 hours. Some studies have demonstrated no significant effect in the prevention of RDS within this time period, but there is still a reduction in perinatal and neonatal deaths, without increasing maternal risks. Therefore, even if delivery is imminent within 48 hours, antenatal steroids should be considered up to 36+6 weeks of gestation.11 12 13
Although it is well established that antenatal magnesium sulphate administered to women at risk of preterm delivery at gestations less than 30 weeks significantly reduces the risk of neonatal cerebral palsy,14 administering the medication during the transfer adds another level of risk of magnesium toxicity. Is there any benefit of just giving a loading dose? Is the risk of the infusion worth the benefit at this gestation?
Numerous protocols exist, both in practice and research, for administration of magnesium sulphate for fetal neuroprotection. Depending on the medical evacuation provider, magnesium sulphate infusion may mandate the presence of a medical staff escort on the flight, rather than a nurse. Once again, this can delay a transfer or limit local medical resources from other patients. Therefore, the risks and benefits must be considered on a case-by-case basis.
As the transport team arrives, the contractions persist, prompting the team to deliberate about commencement of another tocolytic. What tocolytic is available and what are the risks of giving it?
Despite the paucity of evidence between management of threatened preterm labour with tocolytic agents and improved perinatal outcomes,15 they might be useful in temporarily stalling labour in the transfer setting. In addition to nifedipine, intravenous salbutamol is another preferred alternative for a number of transfer providers, especially at more advanced dilatations. However, the increased maternal side effects and complications must be considered and planned for, especially with prolonged use, as evacuations from remote areas of Australia can take in excess of 12 hours.16
Soon the flashing lights of the ambulance fades from view as they head off to the local airfield. You start to relax for the first time today, knowing you made the right decision and appropriate management was underway. As a big gust of wind suddenly sweeps by, your heart skips a beat as you remember what the Royal Flying Doctor Service coordinator said – the cyclone is heading your way! You dash for your car to head to the nearest supermarket to grab bottles of milk and coffee pods, in preparation for the road blocks, as what good is an obstetrician without their morning double-shot flat white?
- Boland RA, Dawson JA, Davis PG, Doyle LW. Why birthplace still matters for infants born before 32 weeks: Infant mortality associated with birth at 22–31 weeks’ gestation in non-tertiary hospitals in Victoria over two decades. ANZJOG. 2015;55(2):163-9.
- Langford SA. The first medical jet aircraft for the Royal Flying Doctor Service. MJA. 2009;191(11-12):609-10.
- Downing SG, Wright R, Marquardt T, Callander E. Use of fetal fibronectin testing in women transferred for threatened preterm labour in remote far north Queensland. ANZJOG. 2018. doi: 10.1111/ajo.12878.
- Porcellato L, Masson G, O’Mahony F, et al. ‘It’s something you have to put up with,’ service users’ experiences of in utero transfer: a qualitative study. BJOG. 2015;122(13):1825-32.
- Chao TT, Bloom SL, Mitchell JS, et al. The diagnosis and natural history of false preterm labor. Obstet Gynecol. 2011;118(6):1301-8.
- Abbott DS, Hezelgrave NL, Seed PT, et al. Quantitative Fetal Fibronectin to Predict Preterm Birth in Asymptomatic Women at High Risk. Obstetrics & Gynecology. 2015;125(5):1168-76.
- Melchor JC, Khalil A, Wing D, et al. Prediction of preterm delivery in symptomatic women using PAMG-1, fetal fibronectin and phIGFBP-1 tests: systematic review and meta-analysis: Prediction of preterm delivery using PAMG-1, fFN and phIGFBP-1 tests. Ultrasound in Obstetrics & Gynecology. 2018;52(4):442-51.
- Gates M, Pillay J, Featherstone R, et al. Effectiveness and Accuracy of Tests for Preterm Delivery in Symptomatic Women: A Systematic Review. J Obstet Gynaecol Can. 2018. doi: 10.1016/j.jogc.2018.06.019.
- Akl N, Coghlan EA, Nathan EA, et al. Aeromedical transfer of women at risk of preterm delivery in remote and rural Western Australia: why are there no births in flight? ANZJOG. 2012;52(4):327-33.
- Melamed N, Shah J, Soraisham A, et al. Association Between Antenatal Corticosteroid Administration-to-Birth Interval and Outcomes of Preterm Neonates. Obstet Gynecol. 2015;125(6):1377-84.
- Roberts D, Brown J, Medley N, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2017;(21)3:CD004454.
- Ahmed MR, Sayed Ahmed WA, Mohammed TY. Antenatal steroids at 37 weeks, does it reduce neonatal respiratory morbidity? A randomized trial. J Matern Fetal Neonatal Med. 201528(12):1486-90.
- Saccone G, Berghella V. Antenatal corticosteroids for maturity of term or near term fetuses: systematic review and meta-analysis of randomized controlled trials. BMJ. 2016;(12)355:i5044.
- Doyle LW, Crowther CA, Middleton P, et al. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev. 2009;21(1):CD004661.
- World Health Organization. WHO recommendations on interventions to improve preterm birth outcomes. Geneva, Switzerland: World Health Organization; 2015.
- Conde-Agudelo A, Romero R, Kusanovic JP. Nifedipine in the management of preterm labor: a systematic review and metaanalysis. Am J Obstet Gynecol. 2011;204(2):134.e1-20.
Well written article Jared. In 2015 I had a case there where the mother with intact membranes was already 6cm dilated, and John Newnham convinced me per phone that they’d “never had a delivery in the plane”. I can’t recall the rest of the details but she got there intact and delivered safely in Perth. I used to get concerned about the RFDS insistence on a Salbutamol infusion even after we had loaded people with Nifedipine. Is that still the protocol and has anyone reviewed the situation of B mimetics on top of Ca channel blockers?
Yes, the RFDS in WA is very proud of that fact, and Prof Newnham has published the paper as listed in the references as to factors why this maybe. He has been noted to state that maybe we just need a plane constantly circling at 35 000 feet with all our PTL patients on it until they hit 39 weeks!
From my recent dealings, the RFDS appear to be happy with just nifedipine if contractions have ceased. However at advanced dilitations, and ongoing contractions they prefer to move to salbutamol. They quote the ability to titrate the infusion and their long term data of never having a delivery in the air, as the main two reasons.
We do have the concern of using both together as you stated, but most of the time we cease one before starting the other with contact normally made with RFDS well before the arrival of their plane. I have had one severe tachycardia and then hypotension mid-flight I was phoned about by the flight crew, which there was concern about the salbutamol being started soon after nifedipine. I am not sure if the two were related. I could not find any trials in a quick search, but a few warning case reports.
Thanks again for your comment.