Multiple births are increasing in frequency related to advanced maternal age and fertility treatments, and they have an increased risk for congenital anomalies compared to singleton births. However, twins have the same congenital anomalies <15% of the time. Thus, having multiple births with discordant anomalies is a growing challenge for neonatologists. Although external anomalies can often be spotted quickly at delivery or sex differences between multiples can rapidly identify those with internal anomalies described on prenatal ultrasound, we present a case of male multiples, who would optimally receive different initial resuscitation strategies on the basis of the presence or absence of an internal anomaly. The similar size of 4 extremely preterm quadruplets raises concern for whether accurate, immediate identification of 1 neonate with a congenital diaphragmatic hernia will be reliable in the delivery room. Clinicians discuss the ethical considerations of an “all for one” approach to this resuscitation.
Cases involving multiple-gestation pregnancies raise unique ethical dilemmas. In some cases, what is good for one fetus or newborn might be bad for the others. The most common such dilemmas arise in twin-twin transfusions or in complex cases of conjoined twins. In this article, we present a situation in which the optimum delivery room treatment of 1 infant among 4 quadruplets might have required potentially harmful treatment of the other 3.
A mother (gravida 3, para 1102) is pregnant with quadruplet boys after in vitro fertilization with 3 embryos. The pregnancy was determined to be trichorionic quadamniotic, with fetuses C and D sharing a placenta early in gestation. The placenta for fetus A was anterior, and the remaining 2 placentas were posterior at that time. With growth and uterine crowding in recent weeks, it has been technically difficult to identify the fetuses on the basis of this. One of the quadruplets (fetus D) has a left congenital diaphragmatic hernia (CDH). Selective fetal reduction is offered and declined by the parents early in the pregnancy. The mother is being monitored as an inpatient because of cervical shortening. A full course of betamethasone was given at 23 weeks’ gestation after discussion with the parents about the risks of short-term and long-term morbidity and mortality in extremely preterm infants.
Comfort care was recommended for quadruplet D with the diaphragmatic hernia if delivery occurred at 23 weeks’ gestation. The parents were not ready to accept or decline this recommendation. Because delivery was not imminent, resuscitation plans were not finalized for quadruplet D.
The mother experiences premature preterm rupture of membranes at 26 4/7 weeks’ gestation, followed by preterm labor. A single repeat dose of betamethasone is administered. A cesarean delivery is planned because of the multiple gestations and breech and transverse lie of all fetuses.
The on-call neonatology team begins to discuss plans for the delivery room management of quadruplet D. However, the practical point is raised of how the team can be sure that they have correctly identified the newborn with the diaphragmatic hernia. All the fetuses are male. There are no other known, external congenital anomalies. The estimated fetal weights performed a few days before the premature preterm rupture of membranes revealed 3 fetuses with weights of 890 to 952 g and fetus D with an estimated weight of 526 g. However, estimated fetal weights are less accurate in multiple-gestation pregnancies. A 15% overestimation could mean that the quadruplets without known anomalies might have birth weights close to 750 g. A 15% underestimation on the fetus with the diaphragmatic hernia could equate with a birth weight of 605 g.
Because a delay of several minutes is not uncommon between delivery of higher-order multiples, resuscitation would need to start before all the newborns could be evaluated side by side to determine who is the smallest. A diaphragmatic hernia should lead to the absence of breath sounds on the left. However, malposition of an endotracheal tube could lead to similar findings. Respiratory distress syndrome causes poor compliance and can make auscultation challenging in an extremely preterm infant, particularly in a busy delivery room with multiple resuscitations proceeding. The team comes to the conclusion that immediately offering palliative care to the fetus with the CDH will be challenging from an identification standpoint. The team meets with the parents again and discusses their current wishes. Although the parents understand the extremely poor prognosis for fetus D, they want him to have a trial of resuscitation.
The team prepares for resuscitation of the quadruplets. The unit’s standard for extremely preterm infants 25 to 28 weeks’ gestation is to attempt stabilization on continuous positive airway pressure (CPAP) as a first-line approach and use intubation only if CPAP fails. However, the standard of care for a diaphragmatic hernia is to intubate immediately to avoid gaseous distension of the stomach and bowel, which would worsen ventilation. Potential difficulty with identification of the newborn with the CDH arises again. Some team members voice that each of the quadruplets should be immediately intubated to properly resuscitate the child with CDH and optimize any chance of survival in this newborn. Others raise concerns that the patient with the CDH is not likely to be vigorous and spontaneously breathing at delivery. The mother was treated with a full course of antenatal corticosteroids and booster dose. If one of the quadruplets cries and has a heart rate >100 beats per minute at delivery, should he be intubated prophylactically as well? Some team members are concerned that stabilization on CPAP became the unit standard to try to avoid lung injury from mechanical ventilation. Should 3 extremely preterm patients be exposed to the ventilator to protect one whose prognosis is likely grave?
Autumn Kiefer, MD, and Greg Barretto Jr, MD, MS, Comments
The case represents a challenge of how to balance beneficence and nonmaleficence between siblings with differing medical needs and a short timeline to intervene. Twins and higher-order multiples have an increased risk of congenital anomalies compared with singletons with an adjusted relative risk of 1.27 (95% confidence interval 1.24–1.30), and multiples are not usually affected by the same anomalies.1 If all the neonates in this case are intubated immediately, fetus D would certainly avoid noninvasive ventilation, which would distend the bowel and further impair lung function. However, it also places what is beneficent for fetus D above what may be optimal for his 3 siblings. The risk for bronchopulmonary dysplasia (BPD) or the combined outcome of BPD or death is decreased with CPAP stabilization,2 so intubating a very low birth weight infant who does not require it may cause an inflammatory response in the lungs and could precipitate rare complications like tracheal perforation. Thus, some harm could occur to 3 neonates to benefit one.
None of the clinicians involved advocate for a severely depressed neonate to be resuscitated with CPAP alone because that would be contradicted by the Neonatal Resuscitation Program standards. However, some clinicians advocate for stabilizing the quadruplets on the basis of their individual clinical conditions, as if we did not know that a CDH was present in one of them. Comparisons are made to a previous clinical situation in which preterm twin girls were of similar birth weights, but one had a ductal-dependent cyanotic congenital heart disease. Both twins had respiratory disease after birth with saturations at ∼90% with minimal supplemental oxygen on CPAP support, necessitating NICU admission. Neither had a murmur present at birth. Thus, the identity of the twin with congenital heart disease was unclear. In that case, the decision was made not to start a prostaglandin infusion prophylactically, as was typically the practice at the time, but rather perform a confirmatory echocardiogram to definitively identify the affected twin. Waiting to administer prostaglandin was done to avoid the potential harm of secondary apnea in the unaffected twin. However, the ductus arteriosus is typically open at birth, and some centers do not routinely start prostaglandin infusion immediately. Thus, although the balance of beneficence and nonmaleficence was at play, the timeline allowed the delivery room team to wait for confirmation of the anomalies without causing any long-term harm or short-term instability. Using the “wait and see” approach with the neonate with CDH presumes that he will either be nonvigorous or will clinically declare himself within minutes of birth. However, any positive pressure breaths given by mask in the initial stabilization effort of the patient with CDH would direct some air to the bowel, make subsequent ventilation more difficult, and thus cause harm. Because an extremely preterm infant with CDH has little reserve, concerns arise that any harm to this neonate could precipitate his death.
If survival at 26 weeks’ gestation with a CDH was sufficiently low as to consider treatment futile, then prioritizing the long-term outcomes of the siblings could be justified. Although prematurity is associated with an increased mortality in patients with CDH, a 2010 report from an international CDH registry included a 31.6% survival for those with CDH born at <28 weeks’ gestation.3 This chance of survival was similar to the survival estimate used by our center at 23 weeks’ gestation, at which time the parents had agreed to steroid treatment.
Julie Johnson Rolfes, MD, Comments
With imminent delivery, there is no time for a prolonged assessment of the case, a formal ethics consultation, or much more discussion with family. With this in mind, we can briefly analyze the case from the perspective of each of the key players and then attempt to balance what is best for each while not inflicting significant harm on any individual.
First, we can reflect on the parents’ perspective. Throughout this pregnancy, they have invested time, finances, and likely a good bit of emotion. They have been counseled several times about the high risk of morbidity and mortality specifically for quadruplet D and more recently about the risks to all the quadruplets when facing delivery so prematurely. The parents continue to desire support for the lives of all of their 4 fetuses, optimizing the chances of survival and survival without morbidity to the extent that medical care can. The team feels (and I agree) that initial resuscitation for all the quadruplets is ethically permissible; thus, parental authority should be respected.
Next, let us evaluate the case on behalf of quadruplets A, B, and C, whose morbidity and mortality risks are less than quadruplet D but not insignificant.4 Newer literature supports efforts to avoid intubation and mechanical ventilation if at all possible because even airway instrumentation is not without potential negative side effects.5 If you prioritize the resuscitation approach that benefits the most individuals, then stabilizing on CPAP per the unit protocol, with intubation only if clinically indicated, would be the best option for these neonates. By minimizing risk to quadruplets A, B, and C, this choice would potentially harm quadruplet D.
Finally, we consider quadruplet D in isolation. His risk of morbidity and mortality is high given the combination of extreme prematurity, multiple gestation with relative growth restriction, and CDH.6,7 Already, because of his size and prematurity, his treatment options are significantly reduced. He would not be a candidate for extracorporeal membrane oxygenation, his surgical treatment options would be significantly limited, and use of therapies such as inhaled nitric oxide would be less evidence based. Even if triplet D survives his first days and weeks of life, providing him adequate nutrition will be complicated by his CDH and extreme prematurity and will likely necessitate prolonged parenteral nutrition. This, in and of itself, carries significant morbidity risk.8,9
In the face of all these constraints, optimizing his care and resuscitation is of utmost importance to improve his chance of survival and decrease the risk of morbidity. Reducing gastric dilation is one available treatment strategy; thus, immediate intubation would be the best practice for this neonate. This fact could be used to justify intubation of all of the quadruplets immediately, reverting to routine stabilization on CPAP only if the team definitively identifies the infant with the CDH before all of the deliveries are completed. Although this strategy prioritizes the care of the sickest infant, the nonstandard care of the infants who are expectedly less sick may increase their risk of harm.
So, what is a just, ethical decision for the family and medical team? I would advocate for routine resuscitation for all 4 quadruplets. This seems to be the safest course of action because varying from the team’s practiced routine and established guidelines introduces more room for inadvertent medical error. In addition, there is a good chance that quadruplets A, B, and C would meet intubation criteria in the delivery room simply on the basis of their gestational age and quadruplet status, and quadruplet D is at an even higher likelihood of meeting intubation criteria during resuscitation even without being able to clinically diagnose his diaphragmatic hernia. Thus, although this approach does slightly increase the risk of quadruplet D not receiving immediate intubation, his increased risk of poor outcome is likely only to be a small adjustment to his already serious morbidity and mortality risks, and the remaining quadruplets are spared unnecessary harm.
With that said, the team should still employ what modalities are available to identify quadruplet D as quickly as possible and decrease his risk of harm. If bedside ultrasound is available and a skilled ultrasonographer and/or radiologist is available to be in the delivery room, this could facilitate rapid identification of the diaphragmatic hernia during active resuscitation and without radiation exposure. Having radiography available would be the second-best option but would be more cumbersome during active resuscitation and would be accompanied by radiation exposure to infants and the medical staff. Regardless of the radiologic technology available, each neonate should be assessed frequently during resuscitation for decreased left-sided breath sounds, scaphoid abdomen, and right-shifted heart sounds as potential indications of left-sided diaphragmatic hernia; however, I agree that these may be subtle, and the sensitivity of auscultation in this sized neonate in a busy resuscitation room is limited. An orogastric tube should be placed as early as possible into each quadruplet, and the stomach should be aspirated regularly to decompress as much air as possible.
Ultimately, in this difficult clinical situation, I believe that parental wishes to support all 4 quadruplets should be respected and that this is best accomplished by following standard resuscitation practices, with urgent identification of quadruplet D and subsequent tailoring of care for his specific medical needs. This approach maximizes benefit and minimizes harm for the largest number of neonates, which I think fits into the parents’ stated goals and the medical team’s responsibilities, as well.
Outcome of the Case
Events progress rapidly around this multiple-gestation delivery. Discussion with the parents focuses on whether palliative care would be offered immediately to quadruplet D. We share with the family our internal conflict of how to balance the needs of each of their sons. The parents share that they had faced the same challenges, being asked about selective reduction in the face of a potentially lethal anomaly and then again to consider palliation at delivery. Ultimately, they want to give their smallest son a chance, even if it means that their entire family faces a greater challenge.
The decision is made to intubate all of the patients, regardless of clinical status, to protect fetus D. The infants deliver over a 4-minute window. Each infant is initially apneic and limp with heart rates <60. The birth weights of neonates A, B, C, and D are 1000, 850, 900, and 520 g, respectively. Quadruplets A and B require extensive resuscitation including chest compressions. Quadruplet C responds to intubation alone. In these infants, bilateral breath sounds are present. Quadruplet D, the smallest neonate, has poor chest rise despite increasing support and never achieves a heart rate >70 beats per minute. The parents are updated with the lack of response to resuscitative efforts in quadruplet D and agree with a transition to palliative care. He dies shortly thereafter in his parents’ arms. The 3 remaining siblings survive with BPD. Each requires home oxygen at hospital discharge.
John D. Lantos, MD, Comments
Although this case is more complex than most, it illustrates a rule that should apply to all decisions involving newborns: avoid making difficult and irreversible decisions about delivery room management prenatally! Fetal diagnosis is imperfect. Prenatal assessments give us clues about what infants will look like at birth, but those clues often turn out to be either wrong or irrelevant. In this case, the treatment would likely have been the same for these 4 infants without the agonizing prenatal discussions. Each infant was assessed at birth, treated on the basis of that assessment, and decisions were then made on the basis of the more firm knowledge of each infant’s condition and prognosis.
Dr Barretto helped to conceptualize the report, led the family discussion to obtain consent for publication of the case, and revised the manuscript; Dr Kiefer helped to conceptualize the report and drafted and revised the manuscript; Dr Johnson Rolfes helped to draft and revise the manuscript and references; Dr Lantos organized the manuscript and wrote sections of and reviewed the final manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
FUNDING: No external funding.
congenital diaphragmatic hernia
continuous positive airway pressure
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.