Sir/Madam,

I read with interest the authors’ description of transient neonatal diabetes mellitus in a pre-term infant. Genetic studies have an important role in the management of these patients. This is an example of pharmacogenetics where the genetic cause of the insulin deficiency determines the response to treatment. It is important that mutations in the ABCC8 are looked for. In a recent case series (1), four of seven mis- sense mutations were familial. Oral sulphonylurea therapy could be effective for most patients with neonatal diabetes caused by a mutant SUR 1. Sulfonylurea therapy is also safe in the short term for patients with diabetes caused by KCNJ11 mutations and is probably more effective than insulin therapy (2). Mutations of KCNJ11 are typically associated with permanent diabetes mellitus, whereas most mutations of ABCC8 are associated with transient diabetes mellitus, perhaps reflecting a less severe form of the disease (1).

There are practical problems when dealing with insulin therapy in infancy. These include the preparation and administration of minute doses of insulin. Insulin comes in a strength of 100 units per ml. To give small doses to a baby, it is necessary to dilute this insulin to 10 units per ml. Only soluble insulin can be diluted with saline. Other forms of insulin need a specific diluent from the manufacturer on a named patient basis (personal communication). This has to be prepared in the aseptic unit and has a limited shelf life. The diluent is not licensed and is provided on a named patient basis. Home blood glucose monitoring has to be performed with a device which can cope with the neonatal haematocrit range. Dietary management would include regular feeds including night feeds and early weaning under strict dietary supervision. The multi- disciplinary team has a crucial role to play in the successful management of these infants.

1. Activating mutations in the ABCC8 Gene in neonatal

Diabetes mellitus

AP Babenko, M Polak, H Cave et al

N Engl J Med 355; 5: 456-466

2. Switching from Insulin to oral sulfonylureas in

patients with Diabetes due to Kir6.2 mutations

ER Pearson, I Flechtner, PR Njolstad et al

N Engl J Med 355; 5: 467-477

O'Donnell et al (1) explain the need for documenting neonatal resuscitation for audit and teaching purposes. Obstetricians make great efforts to monitor the fetus during labour in the hope of being able to intervene when signs of significant fetal hypoxia develop. Intermittent monitoring may be sufficient in low risk women but continuous monitoring is common in hospital units. If fetal distress is detected and the decision for delivery by caesarean section is made, delivery is expected to occur within 30 minutes. (2) Discontinuing monitoring is not acceptable when fetal compromise is suspected but during this time preparations need to be made for delivery such as transfer to the operating theatre and commencing a spinal anaesthetic. Maintaining continuous and documented fetal monitoring is difficult and not usually maintained during these preparations. Once the caesarean is commenced all monitoring ceases. There may therefore be an interval of 15 to 30 minutes during which little is known and nothing is formally documented about the condition of the fetal heart rate. When the baby is delivered in good condition this gap in our knowledge seems of little consequence. However when the neonate requires resuscitation, we do not know whether this represents the condition of the baby when the decision to deliver was made or whether there has been a significant deterioration since then. Even after delivery there is a significant interval when we rely on clinical assessment of the baby. The heart rate is estimated clinically, as are respiration and oxygen levels. Blood pressure measurements are not usually practical in the first few minutes after birth or during resuscitation. Documentation, as O’Donnell et al (1) point out is retrospective and dependant on memory sometimes after a chaotic and stressful event. Therefore we are often faced with more than 45 minutes of poorly documented data on the condition of the fetus and baby to determine the possible causes of a poor outcome.

Similarly in spontaneous or assisted vaginal delivery there is an interval during which we lose documented evidence of the state of the baby. During the second stage continuous monitoring is still possible but requires careful and frequent adjustment of the transducer. Once the head is delivered monitoring is no longer possible. Normally the body will quickly follow a few minutes later but if there is shoulder dystocia this time may extend to over 5 minutes. Once again our lack of knowledge during resuscitation continues.

A review of fatal shoulder dystocia (3) showed that in 50% of these babies who died, there was less than five minutes delay between delivery of the head and body. In only 25% was there evidence of fetal distress. We do not know what happened to the baby’s heart rate from the moment the head delivered.

While it is true that nothing much more may be possible if urgent delivery is already underway, it is a time when we have no good knowledge of the state of the cardiovascular system. This will limit our understanding and opportunity for maximising the management of fetal distress. Video monitoring of resuscitation is one way of improving our understanding. There is a gap which is poorly recognised. With current technology it should be possible to monitor continuously the heart rate once the head is delivered and continue during resuscitation until standard neonatal monitoring is in place or the baby no longer needs it. The convenience of Bluetooth transfer of data from my mobile phone makes me wonder if monitoring need not have the restrictions of wires.

David J R Hutchon FRCOG

References
1. O’Donnell CPF, Omar C, Kamlin F, Davis PG, Morley CJ. Ethical and legal aspects of video recording neonatal resuscitation. Archives of Disease in Childhood - Fetal and Neonatal Edition 2008;93:F82-F84
2. National Institute for Clinical Excellence. Intrapartum Care Guideline September 2007
3. Hope, P., Breslin S, Lamont L, Lucas A, Martin D, Moore I, Pearson J, Saunders D, Settatree R. Fatal shoulder dystocia: a review of 56 cases reported to the Confidential Enquiry into Stillbirths and Deaths in Infancy. Br J Obstet Gynaecol, 1998. 105(12): p. 1256-61.

Sir

We read with interest the original article by Wren et al about the trends in diagnosis of major congenital cardiovascular malformations published in the fetal and neonatal issue of the journal1. The paper discusses the difficulties which we are still experiencing in diagnosing the cardiovascular (CVS) abnormalities. It is evident that we continue to miss life threatening abnormalities despite efforts to improve our detection rates.

The authors in their discussion suggest that better early diagnosis of serious congenital cardiac malformations is likely to be achieved by further improvements in antenatal diagnosis and more wide spread use of routine pulse oximetry. Whether such is indeed the case is open to debate and discussion.

Firstly how can we realistically advance the antenatal detection rate? The current practice is to perform a detailed scan of the foetus at around 19 weeks of gestation to look for foetal abnormalities. This is done by trained sonogarphers who routinely do a 4- chamber view of the heart. The additional view of the outflow tracts is still not routine practice in all units and remains optional. It is envisaged that by obtaining the latter view the detection rate of the CVS malformation would be improved from 25 % to up to 75% as per the RCOG2 guidelines for mid- trimester scans. The malformations which were noted to be undetected in the author’s study include coarctation of the aorta, interruption of the aortic arch, aortic valve stenosis and total anomalous pulmonary venous connection. These malformations are unlikely to be detected on routine anomaly scans and are likely to evolve as the foetus grows. Identifying them may well need another scan later in gestation. This at present is not a recommended practice and has considerable additional resource implications. There is of course the alternative of seeking early input from the experts in cardiac scanning, namely paediatric cardiologists with expertise in foetal cardiac scanning. Again the resource implications make this highly improbable if not impossible. Thus with the current system of screening for foetal abnormalities, we are unsure how the antenatal detection rates for CVS abnormalities can be improved.

Secondly there is paucity of high-quality evidence supporting the role of pulse oximetery for early detection of congenital heart disease. The report of the Tennessee task force, which the authors have referenced in their discussion was based on the analysis of four major studies using pulse oximetry screening3. The task force recommended against mandatory implementation of screening and stated that a very large prospective study is needed to define sensitivity and false positive rates of lower limb pulse oximetry screening in asymptomatic newborn population. More recently a systematic review identified pulse oximetery as a potentially useful tool for diagnosis of congenital heart disease in asymptomatic neonates. The reviewers however in addition concluded that although pulse oximetery is highly specific it has highly variable sensitivity with wide confidence intervals. They also commented on the quality of the various studies included in the review stating that this was generally compromised due to the differential verification used in identifying positive and negative cases. Moreover the absence of blinding, and absent or poor description of the test or reference standard was deemed to have affected the results of the review. The reviewer’s conclusion was that large, well-conducted and robust studies are essential to confirm the value of pulse oximetry as a screening test, in isolation or in combination with clinical examination to obtain precise estimates of its sensitivity4.

It may sound disappointing but it seems rather implausible that detection rates of congenital heart disease in the foetal or neonatal period are going to improve notably in the foreseeable future.

References

1. Wren C, Reinhardt Z, Khawaja K. Twenty-year trends in diagnosis of life-threatening neonatal cardiovascular malformations. Arch Dis Child Fetal Neonatal Ed 2008;93:F33-F35. 2. Ultrasound Screening for Fetal Abnormalities. Report of the RCOG Working Party (2000). RCOG, London. 3. Liske MR, Greeley CS, Law DJ, et al. Report of the Tennessee task force on screening newborn infants for critical congenital heart disease. Pediatrics 2006; 118: e1250–6. 4. Thangaratinam S, Daneils J, Ewer AK, Zamora J, Khan KK. Accuracy of pulse oximetry in screening for congenital heart disease in asymptomatic newborns: as systematic review. Arch Dis Child Fetal Neonatal Ed 2007;92:F176-F180.

Reynolds, like the majority of us neonatologists and obstetricians, would be unable to keep his nerve and delay three minutes before clamping and cutting the cord to be able to proceed with resuscitation. However maintaining a placental circulation may sometimes be all that is required as Aristotle (1) observed “Frequently the child appears to be born dead, when it is feeble and when, before the tying of the cord, a flux of blood occurs into the cord and adjacent parts. Some nurses who have already aquired skill squeeze (the blood) back out of the cord (into the child’s body) and at once the baby, who had previously been as if drained of blood, comes to life again.”

We do not recommend the patience described by Aristotle but some lateral thinking is required. When reversal of tracheal occlusion done in cases of severe congenital diaphragmatic hernias is needed at birth an EXIT (2) procedure is used. Essentially a functional placental circulation is maintained until the tracheal occlusion can be removed and the neonate ventilated.

Resuscitation before the placental circulation has ceased allows some warm oxygenated blood to return to the neonate and supplement oxygenation from the newborns lungs. Indeed as the pulmonary vasculature opens up drawing blood from the rest of the body, the deficit is replaced by redistribution of the returning placental blood. This effect is well recognised as the placental transfusion which occurs in a physiological third stage.(3)

Resuscitation before the cord is clamped and cut takes a little preparation and thought. We have developed a procedure at caesarean section to provide all the normal equipment for resuscitation without compromising the facilities for the neonate or the mother, so that ventilation and pulmonary respiration can be established while the cord remains intact. (4) Precise arrangements may need to be modified according to different theatre layouts. Essentially it involves bringing the resuscitaire up to the side of the operating table. Other approaches are possible. Preparation and cooperation between obstetrician, paediatrician and theatre staff is key to success. There are likely to be substantial benefits for babies with significant hypoxia. When fetal distress is due to cord compression such as with a nuchal cord, the fetus may already be hypovolaemic at birth. Delayed clamping allows time for the placental transfusion to correct the hypovolaemia.

References
1. Aristotle. History of animals. Transl by R Cresswell, London.1878
2. Bouchard S, Johnson MP, Flake AW, et al: The EXIT procedure: Experience and outcome in 31 cases. J pediatr Surg 37(3):418-426, 2002.
3. Linderkamp O. Placental transfusion: determinants and effects. Immediate cord clamping can result in hypotension, hypovolemia and anemia. Clinics in Perinatology 1982;9:559-592
4. Hutchon DJR and Thaker IM. How to resuscitate the neonate with the cord intact at caesarean section. 31st British Congress of Obstetrics and Gynaecology London 6 July 2007