Management premature neonates-Premature Infant: Causes, Complications, and More

Preterm birth , also known as premature birth , is the birth of a baby at fewer than 37 weeks' gestational age , as opposed to the usual about 40 weeks. The cause of preterm birth is often not known. In those at risk, the hormone progesterone , if taken during pregnancy , may prevent preterm birth. Preterm birth causes a range of problems. The main categories of causes of preterm birth are preterm labor induction and spontaneous preterm labor.

Management premature neonates

Google Scholar 9. Quitting smoking, using illegal drugs, or overusing certain prescription drugs. Ibuprofen Prophylaxis [ 46 ]. Reproductive Biomedicine Management premature neonates. Correlation between echocardiographic superior vena cava flow and short-term outcome in infants with asphyxia.

Sex in leather. Introduction

World Health Statistics. Acta Paediatr ; 4 : — Thank you for visiting nature. External link. Biol Neonate ; 56 4 : — New recommendations The nneonates provides an approach to the use of phototherapy and exchange transfusion based on gestation. Pediatric Research Prevention of preterm parturition. J Perinatol ; 28 Management premature neonates — Shapiro SM. Pediatrics ; : e—e Subjects Diseases Paediatrics Therapeutics. All relevant and required headings e.

Stroger Jr.

  • Infants who are born before 37 weeks of completed gestation are at risk of developing a wide range of illnesses, such as intraventricular haemorrhage, bronchopulmonary dysplasia and retinopathy of prematurity, due to the immaturity of many of their physiological systems and processes.
  • Every year 15 million babies are born prematurely.
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Preterm birth , also known as premature birth , is the birth of a baby at fewer than 37 weeks' gestational age , as opposed to the usual about 40 weeks. The cause of preterm birth is often not known. In those at risk, the hormone progesterone , if taken during pregnancy , may prevent preterm birth. Preterm birth causes a range of problems. The main categories of causes of preterm birth are preterm labor induction and spontaneous preterm labor. In contrast to false labour , true labor is accompanied by cervical dilatation and effacement.

Also, vaginal bleeding in the third trimester, heavy pressure in the pelvis, or abdominal or back pain could be indicators that a preterm birth is about to occur. A watery discharge from the vagina may indicate premature rupture of the membranes that surround the baby.

While the rupture of the membranes may not be followed by labor, usually delivery is indicated as infection chorioamnionitis is a serious threat to both fetus and mother. In some cases, the cervix dilates prematurely without pain or perceived contractions, so that the mother may not have warning signs until very late in the birthing process.

A review into using uterine monitoring at home to detect contractions and possible preterm births in women at higher risk of having a preterm baby found that it did not reduce the number of preterm births.

In the U. As NICU care has improved over the last 40 years, the limit of viability has reduced to approximately 24 weeks.

As risk of brain damage and developmental delay is significant at that threshold even if the infant survives, there are ethical controversies over the aggressiveness of the care rendered to such infants. The limit of viability has also become a factor in the abortion debate.

Preterm infants usually show physical signs of prematurity in reverse proportion to the gestational age. As a result, they are at risk for numerous medical problems affecting different organ systems. A study of children born between 22 and 25 weeks who were currently of school age found that 46 percent had severe or moderate disabilities such as cerebral palsy, vision or hearing loss and learning problems.

Thirty-four percent were mildly disabled and 20 percent had no disabilities, while 12 percent had disabling cerebral palsy. The exact cause of preterm birth is difficult to determine and it may be multi-factorial.

Identifying women at high risk of giving birth early would enable the health services to provide specialized care for these women to delay the birth or make sure they are in the best place to give birth for example a hospital with a special care baby unit. Risk scoring systems have been suggested as a possible way of identifying these women.

However, there is no research in this area so it is unclear whether the risk scoring systems would prolong pregnancy and reduce the numbers of preterm births or not.

A number of factors have been identified that are linked to a higher risk of a preterm birth such as being less than 18 years of age. Further, in the U. Pregnancy interval makes a difference as women with a six-month span or less between pregnancies have a two-fold increase in preterm birth. A history of spontaneous i. Adequate maternal nutrition is important. Women with a low BMI are at increased risk for preterm birth. Adequate nutrition is critical for fetal development and a diet low in saturated fat and cholesterol may help reduce the risk of a preterm delivery.

Women with celiac disease have an increased risk of the development of preterm birth. Marital status is associated with risk for preterm birth. A study in Quebec of , births from to revealed less risk of preterm birth for infants with legally married mothers compared with those with common-law wed or unwed parents. Genetic make-up is a factor in the causality of preterm birth. Genetics has been a big factor into why Filipinos have a high risk of premature birth as the Filipinos have a large prevalence of mutations that help them be predisposed to premature births.

Subfertility is associated with preterm birth. The use of fertility medication that stimulates the ovary to release multiple eggs and of IVF with embryo transfer of multiple embryos has been implicated as an important factor in preterm birth. Maternal medical conditions increase the risk of preterm birth. Often labor has to be induced for medical reasons; such conditions include high blood pressure , [48] pre-eclampsia , [49] maternal diabetes, [50] asthma, thyroid disease, and heart disease. In a number of women anatomical issues prevent the baby from being carried to term.

Some women have a weak or short cervix [48] the strongest predictor of premature birth [51] [52] [53] Women with vaginal bleeding during pregnancy are at higher risk for preterm birth. While bleeding in the third trimester may be a sign of placenta previa or placental abruption — conditions that occur frequently preterm — even earlier bleeding that is not caused by these conditions is linked to a higher preterm birth rate.

Anxiety [55] and depression have been linked to preterm birth. Finally, the use of tobacco , cocaine , and excessive alcohol during pregnancy increases the chance of preterm delivery. The World Health Organization published an international study in March Presence of anti-thyroid antibodies is associated with an increased risk preterm birth with an odds ratio of 1.

A systematic review of 30 studies on the association between intimate partner violence and birth outcomes concluded that preterm birth and other adverse outcomes, including death, are higher among abused pregnant women than among non-abused women.

The frequency of infection in preterm birth is inversely related to the gestational age. Mycoplasma genitalium infection is associated with increased risk of preterm birth, and spontaneous abortion. Infectious microorganisms can be ascending, hematogeneous, iatrogenic by a procedure, or retrograde through the Fallopian tubes. From the deciduas they may reach the space between the amnion and chorion , the amniotic fluid , and the fetus.

A chorioamnionitis also may lead to sepsis of the mother. Fetal infection is linked to preterm birth and to significant long-term handicap including cerebral palsy.

It is opined that bacterial vaginosis before or during pregnancy may affect the decidual inflammatory response that leads to preterm birth. Untreated yeast infections are associated with preterm birth. A review into prophylactic antibiotics given to prevent infection in the second and third trimester of pregnancy 13—42 weeks of pregnancy found a reduction in the number of preterm births in women with bacterial vaginosis.

These antibiotics also reduced the number of waters breaking before labor in full-term pregnancies, reduced the risk of infection of the lining of the womb after delivery endometritis , and rates of gonococcal infection. However, the women without bacterial vaginosis did not have any reduction in preterm births or pre-labor preterm waters breaking. Much of the research included in this review lost participants during follow-up so did not report the long-term effects of the antibiotics on mothers or babies.

A number of maternal bacterial infections are associated with preterm birth including pyelonephritis , asymptomatic bacteriuria , pneumonia , and appendicitis.

A review into giving antibiotics in pregnancy for asymptomatic bacteriuria urine infection with no symptoms found the research was of very low quality but that it did suggest that taking antibiotics reduced the numbers of preterm births and babies with low birth weight.

A different review found that preterm births happened less for pregnant women who had routine testing for low genital tract infections than for women who only had testing when they showed symptoms of low genital tract infections.

Also periodontal disease has been shown repeatedly to be linked to preterm birth. There is believed to be a maternal genetic component in preterm birth. However, the occurrence of preterm birth in families does not follow a clear inheritance pattern, thus supporting the idea that preterm birth is a non-Mendelian trait with a polygenic nature. Placental alpha microglobulin-1 PAMG-1 has been the subject of several investigations evaluating its ability to predict imminent spontaneous preterm birth in women with signs, symptoms, or complaints suggestive of preterm labor.

Fetal fibronectin fFN has become an important biomarker—the presence of this glycoprotein in the cervical or vaginal secretions indicates that the border between the chorion and deciduas has been disrupted.

A positive test indicates an increased risk of preterm birth, and a negative test has a high predictive value.

Obstetric ultrasound has become useful in the assessment of the cervix in women at risk for premature delivery. In humans, the usual definition of preterm birth is birth before a gestational age of 37 complete weeks. One of the main organs greatly affected by premature birth is the lungs. The lungs are one of the last organs to mature in the womb; because of this, many premature babies spend the first days and weeks of their lives on ventilators.

Therefore, a significant overlap exists between preterm birth and prematurity. Generally, preterm babies are premature and term babies are mature. Preterm babies born near 37 weeks often have no problems relating to prematurity if their lungs have developed adequate surfactant , which allows the lungs to remain expanded between breaths.

Sequelae of prematurity can be reduced to a small extent by using drugs to accelerate maturation of the fetus, and to a greater extent by preventing preterm birth. Historically efforts have been primarily aimed to improve survival and health of preterm infants tertiary intervention. Such efforts, however, have not reduced the incidence of preterm birth. Increasingly primary interventions that are directed at all women, and secondary intervention that reduce existing risks are looked upon as measures that need to be developed and implemented to prevent the health problems of premature infants and children.

Adoption of specific professional policies can immediately reduce risk of preterm birth as the experience in assisted reproduction has shown when the number of embryos during embryo transfer was limited. The EUROPOP study showed that preterm birth is not related to type of employment, but to prolonged work over 42 hours per week or prolonged standing over 6 hours per day.

Additional support during pregnancy does not appear to prevent low birthweight or preterm birth. Screening for asymptomatic bacteriuria followed by appropriate treatment reduces pyelonephritis and reduces the risk of preterm birth. Self-care methods to reduce the risk of preterm birth include proper nutrition, avoiding stress, seeking appropriate medical care, avoiding infections, and the control of preterm birth risk factors e.

Self-monitoring vaginal pH followed by yogurt treatment or clindamycin treatment if the pH was too high all seem to be effective at reducing the risk of preterm birth. Women are identified to be at increased risk for preterm birth on the basis of their past obstetrical history or the presence of known risk factors.

Preconception intervention can be helpful in selected patients in a number of ways. Patients with certain uterine anomalies may have a surgical correction i. In multiple pregnancies , which often result from use of assisted reproductive technology , there is a high risk of preterm birth.

Selective reduction is used to reduce the number of fetuses to two or three. A number of agents have been studied for the secondary prevention of indicated preterm birth.

Trials using low-dose aspirin , fish oil , vitamin C and E, and calcium to reduce preeclampsia demonstrated some reduction in preterm birth only when low-dose aspirin was used. A randomized trial showed a significant decline in preterm birth rates, [] and further studies are in the making. While antibiotics can get rid of bacterial vaginosis in pregnancy, this does not appear to change the risk of preterm birth. Progestogens , often given in the form of progesterone or hydroxyprogesterone caproate , relaxes the uterine musculature, maintains cervical length, and has anti-inflammatory properties, and thus exerts activities expected to be beneficial in reducing preterm birth.

Progestogen supplementation also reduces the frequency of preterm birth in pregnancies where there is a short cervix. In preparation for childbirth , the woman's cervix shortens.

Preterm cervical shortening is linked to preterm birth and can be detected by ultrasonography. Cervical cerclage is a surgical intervention that places a suture around the cervix to prevent its shortening and widening.

High-dose intravenous immune globulin therapy for hyperbilirubinemia caused by Rh hemolytic disease. Criteria for exchange transfusion in jaundiced newborns. Preterm infant management guideline package Note: This guideline is currently under review. Roberts D, Dalziel S. Nature Research menu. Elevated direct-reacting or conjugated bilirubin levels There are no good data to guide the clinician in dealing with the occasional infant who has a significant elevation of direct-reacting or conjugated bilirubin.

Management premature neonates

Management premature neonates

Management premature neonates

Management premature neonates

Management premature neonates

Management premature neonates. Risk Factors Preterm Delivery

There have been attempts to design a stratification tool to determine the risk of preterm delivery based on risk factors Table 1 7. For instance, the rate of preterm delivery differs greatly between black and white women, with preliminary data showing a rate of History of cervical conization or a loop electrosurgical excision procedure of the cervical transformation zone. Sexually transmitted infections i. Information from reference 7.

Unmodifiable risk factors include a shortened cervix less than 25 mm before 28 weeks' gestation and a history of preterm delivery. The relative risk [RR] is 6. Other preventive strategies that have not shown benefit include vitamin C, vitamin E, bed rest, hydration, and home contraction monitoring. Progesterone supplementation is beneficial in these women starting at 16 to 24 weeks' gestation and continuing through 34 weeks' gestation.

Food and Drug Administration has approved hydroxyprogesterone caproate Makena , mg intramuscularly, as weekly injections. Cervical cerclage, an encircling suture placed around the cervix before or during pregnancy, has been used to help correct structural defects or cervical weakening in high-risk women with a shortened cervix. Studies have shown that cerclage is associated with a decrease in preterm delivery and in perinatal death when used in women with a prior preterm delivery and a cervical length of 25 mm or less.

One trial evaluated the use of cervical pessary and found that the rate of delivery before 34 weeks' gestation was significantly lower in women with a pessary vs. The RR of preterm delivery increases with decreasing cervical length. There is concern about its cost-effectiveness, the availability of quality imaging for all patients, and the possibility of unnecessary interventions.

If screening is performed, cervical length should be measured transvaginally by a qualified ultrasonographer. Unless delivery seems imminent, a digital vaginal examination should be avoided because it could increase the risk of infection. A sterile speculum examination should be performed for further risk stratification, including evaluation for cervical dilation, vaginal infections, bleeding, and rupture of membranes.

Because infections have been associated with preterm delivery, patients should be tested for sexually transmitted infections and group B streptococcal infection. A urine sample should be collected to check for urinary tract infection. A positive nitrazine test result pH of 7. Tests for amniotic proteins, such as placental alpha microglobulin-1 Amnisure , have high reported sensitivity for premature rupture of membranes.

Fetal compromise, clinical chorioamnionitis, and significant abruptio placentae are clear indications for delivery. Preterm labor is diagnosed when a patient is having regular uterine contractions that are accompanied by progressive dilation and cervical effacement. Table 2 summarizes the initial assessment of women with preterm contractions. History of leaking fluid: observed leakage or pooling of fluid from cervical os on sterile speculum examination.

Positive nitrazine test result. Arborization or ferning of fluid on microscopy. Positive amniotic protein test result e. Ultrasound assessment shows low amniotic fluid. Ultrasound-guided transabdominal instillation of indigo carmine dye into the amniotic sac, if available, shows dye outside of the amniotic sac. Observe for regular contractions accompanied by progressive dilation and cervical effacement.

Evaluate for group B streptococcus carrier status, urinary tract infection, bacterial vaginosis, and sexually transmitted infections trichomoniasis, gonorrhea, or chlamydia ; treat as appropriate. Adapted with permission from Sayres WG Jr. Preterm labor. Am Fam Physician. When further evaluation is necessary to predict the likelihood of a preterm delivery, fetal fibronectin testing and cervical length ultrasonography may be helpful. Fetal fibronectin is a glycoprotein produced by amniocytes and cytotrophoblasts.

It appears in cervical secretions before the onset of labor. The fetal fibronectin test has a high negative predictive value. A patient who tests negative has a low probability of delivery within the next 14 days. Once preterm labor is confirmed, a single course of corticosteroids is the only intervention for improving neonatal outcomes. The use of corticosteroids is associated with decreased neonatal morbidity and mortality. Because of its neuroprotective effect, administration of antenatal magnesium sulfate has been associated with a decrease in occurrence and severity of cerebral palsy in infants.

The role of tocolytic agents Table 3 21 , 41 , 42 is to prolong the time to delivery so that antenatal corticosteroids and potentially magnesium sulfate can be administered, and the mother can be transferred to a tertiary care facility with a neonatal intensive care unit.

Tocolytics have not been shown to directly improve neonatal outcomes, 21 and they are not always indicated. Nifedipine calcium channel blockers 21 , Dizziness, flushing, and hypotension; suppression of heart rate, contractility, and left ventricular systolic pressure when used with magnesium sulfate; elevation of hepatic transaminase levels.

Hypotension and preload-dependent cardiac lesions, such as aortic insufficiency. Nausea, esophageal reflux, gastritis, emesis; platelet dysfunction is rarely of clinical significance in patients without an underlying bleeding disorder.

In utero constriction of ductus arteriosus, oligohydramnios, necrotizing enterocolitis in preterm newborns, patent ductus arteriosus in infants. Platelet dysfunction or bleeding disorder, hepatic dysfunction, gastrointestinal ulcerative disease, renal dysfunction, asthma in women with hypersensitivity to aspirin. Terbutaline beta-adrenergic receptor agonist 21 , Alternate dosage: 2.

Tachycardia, hypotension, tremor, palpitations, shortness of breath, chest discomfort, pulmonary edema, hypokalemia, and hyperglycemia. Magnesium sulfate 21 , Flushing, diaphoresis, nausea, loss of deep tendon reflexes, respiratory depression, and cardiac arrest; suppression of heart rate, contractility, and left ventricular systolic pressure; produces neuromuscular blockade when used with calcium channel blockers.

Information from references 21 , 41 , and First-line agents used to delay delivery up to 48 hours include calcium channel blockers e. Caution must be used if combining magnesium sulfate with beta-adrenergic receptor agonists or calcium channel blockers because of possible maternal complications. Tocolysis is generally avoided in the presence of fetal distress, chorioamnionitis, or maternal instability. Reprinted with permission from practice bulletin no.

Obstet Gynecol. Intrauterine bacterial infections are associated with preterm labor, especially before 32 weeks' gestation. Although several trials have been conducted, no studies have shown that use of antibiotics during preterm labor is effective in delaying delivery or reducing neonatal morbidity associated with preterm delivery.

Search dates: March 30 to April 1, ; July 21, ; and November 15 to 18, Already a member or subscriber? Log in. Reprints are not available from the authors. Births: final data for Natl Vital Stat Rep. Births: preliminary data for Practice bulletin no.

American College of Obstetricians and Gynecologists. ACOG committee opinion no. A multistate quality improvement program to decrease elective deliveries before 39 weeks of gestation [published correction appears in Obstet Gynecol. Association of preterm delivery with long-term survival, reproduction, and next-generation preterm delivery [published correction appears in JAMA. Epidemiology and causes of preterm delivery.

Risk-scoring systems for predicting preterm delivery with the aim of reducing associated adverse outcomes. Cochrane Database Syst Rev. The length of the cervix and the risk of spontaneous premature delivery.

N Engl J Med. Spong CY. Prediction and prevention of recurrent spontaneous preterm delivery. Recurrence risk for preterm delivery. Am J Obstet Gynecol. Vaginal progesterone reduces the rate of preterm delivery in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial.

Ultrasound Obstet Gynecol. Cervical pessary in pregnant women with a short cervix PECEP : an open-label randomised controlled trial [published correction appears in Lancet. Low pregravid body mass index as a risk factor for preterm delivery: variation by ethnic group. The association between prepregnancy maternal body mass index and preterm delivery. Am J Perinatol. Preterm delivery after surgical treatment for cervical intraepithelial neoplasia [published correction appears in Obstet Gynecol.

Treatment for cervical intraepithelial neoplasia and risk of preterm delivery. Treatment of periodontal disease during pregnancy: a randomized controlled trial.

Frequency of uterine contractions and the risk of spontaneous preterm delivery [published correction appears in N Engl J Med. Effect of a cholesterol-lowering diet on maternal, cord, and neonatal lipids, and pregnancy outcome: a randomized clinical trial. Keirse MJ. Progestogen administration in pregnancy may prevent pre-term delivery. Br J Obstet Gynaecol.

This in turn places them at increased risk of poor physical and neurodevelopmental health outcomes, such as blindness, deafness and cerebral palsy.

Delivery of care to these vulnerable infants should be specifically targeted to minimize these risks and optimise outcomes for these children. This guideline package has been complied to support medical, nursing and allied health staff in their provision of high quality, evidence-based care to our preterm infant cohort to ensure they achieve the best health outcomes possible.

The Preterm Infant Management Guideline Package is comprised of multiple separate guidelines covering a variety of important aspects of preterm infant care.

All relevant and required headings e. Please remember to read the disclaimer. Updated September

Patent Ductus Arteriosus in Premature Neonates

Stroger Jr. Persistent patency of the ductus arteriosus is a major cause of morbidity and mortality in premature infants. In infants born prior to 28 weeks of gestation, a hemodynamically-significant patent ductus arteriosus PDA can cause cardiovascular instability, exacerbate respiratory distress syndrome, prolong the need for assisted ventilation, and increase the risk of bronchopulmonary dysplasia, intraventricular hemorrhage, renal dysfunction, intraventricular hemorrhage, cerebral palsy, and mortality.

In this article, we review the pathophysiology, clinical features, and assessment of hemodynamic significance, and provide a rigorous appraisal of the quality of evidence to support current medical and surgical management of PDA of prematurity. Cyclo-oxygenase inhibitors such as indomethacin and ibuprofen remain the mainstay of medical therapy for PDA, and can be used both for prophylaxis as well as rescue therapy to achieve PDA closure.

Surgical ligation is also effective and is used in infants who do not respond to medical management. Although both medical and surgical treatment have proven efficacy in closing the ductus , both modalities are associated with significant adverse effects. In this article, we review the clinical features and management of persistent patent ductus arteriosus PDA in premature infants. The ductus arteriosus undergoes functional closure within a few hours after birth due to constriction of the medial smooth muscle layer.

With the cessation of the ductal shunt between the systemic and pulmonary circulation, the right ventricular output is now no longer diverted to the aorta and flows directly into the pulmonary circulation. The consequent increase in venous return from the lungs raises the left atrial pressures, closing the other right to left shunt of fetal life across the foramen ovale in the inter-atrial septum. In premature infants, the normal process of ductal closure is often delayed or interrupted.

As the pulmonary vascular resistance falls after birth, blood is increasingly shunted away from the aorta into the pulmonary artery, resulting in pulmonary overcirculation with frequent exacerbation of lung disease and increased risk of pulmonary hemorrhage and BPD[ 9 - 20 , 31 ].

A hemodynamically-significant PDA is frequently marked by additional clinical signs such as an active precordium, bounding pulses, wide pulse pressure [ 28 ], and radiological signs such as cardiomegaly, prominent pulmonary vascular markings, dilatation of the left atrium, and a horizontalized left main bronchus [ 6 , 37 ]. As the shunt size increases, the electrocardiogram may also show signs of left ventricular hypertrophy and left atrial enlargement [ 6 ].

Echocardiography is the mainstay of diagnosis and assessment of PDA. It allows direct visual assessment of the ductus originating from the descending aorta distal to the left subclavian artery and connecting to the main pulmonary artery [ 34 ]. Doppler flow studies can confirm ductal patency and help assess the direction of ductal flow, cardiac anatomy, ventricular function, the ratio of estimated pulmonary to systemic blood flow [ 40 ], and pulmonary artery pressures [ 6 ].

Echocardiography can also be useful in predicting the clinical course; the ductal size on day PDA:LPA ratio is a useful predictor of a hemodynamically-significant PDA, antedating the onset of clinical signs by up to days [ 41 ]. Although no laboratory tests can reliably indicate the presence of a PDA, circulating levels of B-type natriuretic peptide BNP , a hormone secreted by the ventricles under hemodynamic stress and congestive heart failure, can be both sensitive and specific for detecting a hemodynamically-significant PDA and for monitoring response to therapy [ 42 , 43 ].

In a prospective blinded study, Sanjeev et al. Further study is needed in larger cohorts to determine whether BNP levels in early neonatal period can help differentiate between candidates for expectant vs. Medical management of PDA in a premature infant is comprised of fluid restriction, cyclo-oxygenase COX inhibitors such as indomethacin and ibuprofen lysine, and, occasionally, cautious use of diuretics in symptomatic infants [ 44 , 45 ].

There has been considerable variability in the dosing regimens for the two drugs; Table 2 summarizes dosing regimens for indomethacin and ibuprofen lysine used for prophylactic and rescue therapy.

Short 3-dose course of prophylactic indomethacin 0. Extended 6-dose course 0. The procedure is generally well-tolerated and is considered by some as a preferred first line of treatment in preterm infants who are less likely to respond to indomethacin, such as those weighing less than grams with a large left atrial-aortic root ratio on echocardiography [ 47 - 52 ].

Surgical ligation of a hemodynamically-significant PDA can improve hemodynamics, lung compliance, and reduce the duration of mechanical ventilation [ 53 , 54 ]. Offered as a prophylactic therapy, surgical ligation was effective in preventing NEC [relative risk RR 0. Complications of PDA ligation include pneumothorax, hypothermia, intra-operative bleeding, phrenic nerve palsy, wound infection, vocal cord palsy and thoracic scoliosis [ 47 , 56 , 57 ].

Although the efficacy of both COX inhibitors as well as surgery in ensuring ductal closure is well-established, a consensus on the choice of medical vs. Gersony et al. The surgical group had a higher incidence of pneumothorax [RR 2. Three recent observational studies have reported that infants receiving surgical ligation of PDA may be at increased risk of adverse outcomes such as chronic lung disease, ROP, and neurosensory impairment [ 59 - 61 ].

In some studies, surgical ligation was also associated with increased cardiorespiratory morbidity in the immediate post-operative period [ 59 , 62 ]. In a study of 3, infants weighing less than grams, Lee et al.

Fowlie et al. The benefit of prophylactic indomethacin in reducing pulmonary hemorrhage, a known association of PDA [ 13 , 14 ], remains unclear. In a study published in abstract form only, Domanico et al. In a study of infants, Alfaleh et al.

Prophylactic indomethacin did not change respiratory outcomes or the incidence of pulmonary hemorrhage, gastrointestinal perforations, NEC, severe bleeding, or sepsis.

Treated infants had a higher incidence of oliguria RR 1. In an effort to restrict the use of indomethacin and limit the possibility of adverse effects to patients with greater chance of benefit, some studies have targeted infants with an asymptomatic PDA instead of treating all premature infants prophylactically. Several dosing regimens of indomethacin have been used for prophylaxis and treatment of PDA Table 2.

The rate of clinical reopening of ductus may be higher in infants with a birth weight less than grams and if echocardiography shows residual luminal flow [ 78 , 79 ]. The choice of the hour dosing intervals in indomethacin therapy is largely empirical.

In a retrospective study, Rosito et al. Although there was a trend towards a higher rate of PDA closure and a lower need for surgical ligation of the ductus with the hour dosing regimen, the differences did not reach statistical significance. The study also did not evaluate for the frequency of adverse effects in the two treatment groups.

Several studies have evaluated continuous infusions of indomethacin as a strategy to minimize adverse effects. Yoshimoto et al. There was no difference in mortality and early neonatal morbidities in the two groups. Similarly, in meta-analysis [ 82 ] of data from two trials [ 76 , 83 ], there was no difference in the efficacy or safety of continuous vs. The frequency of ductal reopening and of adverse effects such as oliguria, azotemia, IVH, NEC, or mortality was also similar between the two groups.

In a study of infants weighing less than grams with a clinically-symptomatic PDA, Richards et al. In other studies, oral and intravenously-administered ibuprofen may achieve a similar efficacy in ductal closure. Gokmen et al. The investigators detected a higher rate of PDA closure in the oral ibuprofen group compared to intravenous ibuprofen group Infants receiving intravenous ibuprofen did not show these changes.

Ibuprofen has also been used for prophylaxis against PDA. Ohlsson et al. Ibuprofen also negatively affected renal function. Jones et al. Included studies [ 44 , 58 , 74 - 76 , 88 - 97 ] compared intravenous indomethacin vs. Both intravenous indomethacin RR 2. Other studies [ 98 , 99 ] have shown a similar efficacy of the two drugs. They did not find a significant difference between the two groups RR 0.

Little et al. The proportion of infants with oliguria was also significantly lower in the ibuprofen group RR 0. These differences in renal toxicity are consistent with physiological studies that show greater impairment of renal perfusion when exposed to indomethacin as compared to ibuprofen [ 91 , 92 , , ].

There were no differences in infants treated with indomethacin or ibuprofen in bilirubin levels, IVH, NEC, ROP, sepsis, rate of surgical ligation, length of hospital stay, or mortality. Pharmacotherapy for PDA has been shown to be efficacious in achieving ductal closure but is associated with notable side effects. Studies evaluating COX inhibitors for treatment of neonatal PDA are frequently limited by small sample size and lack of precision, making it difficult to draw strong conclusions regarding dosing regimens, comparative efficacy, and safety profiles of the drugs.

Although both COX inhibitors and surgery are highly effective in closing the ductus , the routine use of COX inhibitors in preterm infants is now being increasingly questioned: RCTs show little evidence of benefit when used for the treatment of PDA; prophylactic COX inhibitor therapy has not improved neurodevelopmental outcome; COX inhibitors are associated with significant side effects; and there is a high potential for spontaneous ductal closure [ - ].

Medical management of PDA in premature infants is comprised of fluid restriction and cyclo-oxygenase COX inhibitors such as indomethacin and ibuprofen lysine.

In selected cases, surgical ligation of the ductus is also an option. National Center for Biotechnology Information , U. Author manuscript; available in PMC May Olachi J. Pham , 3 Kirsten H. Ohler , 3 and Akhil Maheshwari 1. Jennifer T. Kirsten H. Author information Copyright and License information Disclaimer. Copyright notice. The publisher's final edited version of this article is available at Drugs. See other articles in PMC that cite the published article. Abstract Persistent patency of the ductus arteriosus is a major cause of morbidity and mortality in premature infants.

Keywords: ductus, cyclo-oxygenase, congestive cardiac failure, indomethacin, ibuprofen. Pathophysiology of PDA The ductus arteriosus undergoes functional closure within a few hours after birth due to constriction of the medial smooth muscle layer. Open in a separate window. Management of Neonatal PDA Medical Treatment of PDA Medical management of PDA in a premature infant is comprised of fluid restriction, cyclo-oxygenase COX inhibitors such as indomethacin and ibuprofen lysine, and, occasionally, cautious use of diuretics in symptomatic infants [ 44 , 45 ].

Drug Dosing Regimen Indomethacin Prophylaxis [ 12 , 54 , 74 - 76 ] Short 3-dose course of prophylactic indomethacin 0. Medical vs. Surgical Therapy for PDA Although the efficacy of both COX inhibitors as well as surgery in ensuring ductal closure is well-established, a consensus on the choice of medical vs. Prophylactic vs.

Dosing regimens for indomethacin Several dosing regimens of indomethacin have been used for prophylaxis and treatment of PDA Table 2. Indomethacin vs. Adverse effects of indomethacin vs.

Management premature neonates

Management premature neonates

Management premature neonates