Transplacental Transmission

Although viremia and transplacental transmission appear to be rare with human influenza,Reference Irving, James and Stephenson28Reference McGregor, Burns, Levin, Burlington and Meiklejohn29Reference Zou30Reference Gu, Xie and Gao31Reference Yawn, Pyeatte, Joseph, Eichler and Garcia-Bunuel32 the probability of virus reaching the uterus and placenta might be greater for highly pathogenic strains of influenza or in cases of severe maternal illness. For example, evidence of transplacental transmission of avian influenza A (H5N1), as well as several other strains of influenza A virus, has been reported.Reference McGregor, Burns, Levin, Burlington and Meiklejohn29Reference Gu, Xie and Gao31Reference Yawn, Pyeatte, Joseph, Eichler and Garcia-Bunuel32 Limited reports of transplacental transmission may be due, in part, to the challenges in obtaining relevant specimens and appropriate documentation of emerging infections in placental and fetal tissues.Reference Rasmussen, Hayes, Jamieson and O’Leary33

During the pandemic, one report described possible placental transmission of pH1N1 to a newborn from a mother who became ill seven days before delivery.Reference Dulyachai, Makkoch and Rianthavorn34 The newborn was delivered by emergency cesarean section at 31 weeks' gestation after the mother experienced cardiopulmonary failure. Real-time reverse transcription polymerase chain reaction of the newborn's throat swab specimen collected after birth (timing not otherwise reported) confirmed infection with the novel virus. As the mother required intensive cardiopulmonary support at the time of delivery and was not otherwise in contact with her newborn, the authors concluded that the newborn was infected in utero. Although possible, transmission through respiratory droplets cannot be definitely ruled out, because the authors did not report how soon after birth the positive specimen was collected nor whether the newborn was exposed to other infected individuals (eg, health care worker).

Transmission During or After Birth via Contact with Infected Respiratory Droplets

Transmission of pH1N1 via exposure to infected respiratory secretions from a mother with intrapartum infection posed a potential serious risk to the newborn, given the close contact that occurs between mother and child immediately after birth and during the postpartum period. Although mother-to-child transmission of influenza during the intrapartum or early postpartum period had not been systematically examined, there were reports of newborn influenza infection that was thought to have been transmitted via an ill mother after birth. One study examined the risk of influenza during the first year of life among 209 infants enrolled at birth; one death occurred in an 11-day-old newborn with influenza A (H3N2) and pneumonitis.Reference Glezen, Taber, Frank, Gruber and Piedra35 The mother of the newborn had become ill with the influenza virus six days postpartum; the infant did not have any detectable antibody to the virus in cord serum obtained at birth. In another report, a preterm infant who developed severe respiratory distress at age 17 days tested positive for influenza B infection and died at age 33 days.Reference van den Dungen, van Furth, Fetter, Zaaijer and van Elburg36 Although the source of infection was not definitely determined, the newborn's mother experienced symptoms of an influenza-like illness when the newborn was aged 14 days. At the time of the pandemic, only one report, conducted in Australia and New Zealand, had described findings from pH1N1 testing of neonates born to mothers admitted to an intensive care unit during pregnancy or the early postpartum period for pH1N1 illness.7 In that report, 2 (10%) of 20 newborns of critically ill mothers tested for pH1N1 had documented infection with the novel virus. Unfortunately, no other information on the infected newborns was available, including degree of exposure to their ill mothers, timing of testing, presentation of symptoms, or course of illness.

In addition, no reports, to our knowledge, systematically quantified the rate of influenza transmission to newborns from other infected persons such as family members or health care personnel. One case report described influenza B-associated death in a preterm newborn who was thought to have acquired infection from his ill father who visited the neonatal intensive care unit (NICU) while experiencing influenza-like illness.Reference Yusuf, Soraisham and Fonseca37 There is also one report of pH1N1 infection in a 20-month-old oncology patient admitted to the hospital for induction chemotherapy who developed influenza symptoms and tested positive for pH1N1 after being in the hospital for one week.Reference Cunha, Thekkel and Krilov38 As a contact investigation revealed that none of the patient's family members or visitors had been in recent or close contact with anyone experiencing influenza-like illness, and because health care personnel caring for the patient had also cared for pH1N1 patients, the authors concluded that transmission likely occurred through health care personnel. Any ill caregiver in close contact with newborns should be considered a potential source of infection.

Similarly, an infected newborn in a nursery may theoretically pose an infection risk to other newborns. It is estimated that 1% of infants requiring care in the NICU acquire a viral infection after admission to the NICU.Reference Verboon-Maciolek, Krediet, Gerards, Fleer and van Loon39 Most health care-associated viral infections that occur in the NICU are thought to be transmitted through respiratory droplets, contact with the contaminated hands of health care personnel or other adults, and contaminated medical equipment or supplies.Reference Ravenscroft and Weisman40 Specific to influenza virus, there have been several reports of health care-associated influenza virus type A respiratory infection outbreaks in NICUs.Reference Cunney, Bialachowski, Thornley, Smaill and Pennie41Reference Munoz, Campbell and Atmar42Reference Sagrera, Ginovart and Raspall43 Although the NICU patients affected in these outbreaks had underlying conditions and required prolonged hospitalizations and were not likely comparable to healthy newborns not requiring NICU care, novel virus strains for which there is no neonatal passive immunity may impact healthy newborns more readily than other strains. During the pandemic, there were no published reports on the rate of health care-associated infections with influenza viruses among healthy newborns.

Immunization

Perhaps the most important strategy to protect fetuses/newborns from novel influenza infections, including pH1N1, is vaccination of pregnant women, household contacts of infants and pregnant women, and other individuals who will come into close contact with or care for newborns, including health care personnel. For pH1N1, the Advisory Committee on Immunization Practices identified pregnant women, persons who live with or provide care for infants younger than age six months, and health care personnel as three of five initial target groups for pH1N1 vaccination efforts.44 Nevertheless, data collected during the pandemic found low vaccination coverage rates among these target groups: 38.0% for pregnant women, 22.3% for health care personnel, and 13.9% for adults who live with or provide care for infants aged younger than six months.45 For pregnant women, low influenza vaccination rates may be due in part to provider barriers, as findings from one survey of obstetrician-gynecologists found that although the majority would recommend influenza vaccination for a healthy pregnant woman, over one-third did not offer it in their practices.46 Inactivated influenza vaccines have been shown to be safe and effective when administered during pregnancy.Reference Tamma, Ault, del Rio, Steinhoff, Halsey and Omer47

Vaccinating pregnant women not only reduces the likelihood of severe maternal illness and death but also may provide some protection against infection in newborns as a result of maternal antibodies passively transferred via the placenta.Reference Garvy15 One study conducted in Bangladesh randomized receipt of inactivated seasonal influenza vaccine among 340 women in the third trimester of pregnancy during the 2004-2005 influenza season. Findings showed fewer cases of laboratory-confirmed influenza among infants of mothers who received the influenza vaccine than among infants of mothers who did not.Reference Zaman, Roy and Arifeen48 In the United States, a nonrandomized, controlled, observational study was conducted during three influenza seasons during 2002-2005. Maternal influenza vaccination during pregnancy was found to be significantly associated with reduced risk of infant influenza virus infection and hospitalization for an influenza-like illness up to six months of age.Reference Eick, Uyeki and Klimov49 To improve vaccination rates among pregnant women, all health care providers are urged to provide influenza vaccine to pregnant women who present for care. Before hospital discharge, previously unvaccinated mothers should be vaccinated, and vaccine should be offered to family members and other potential close contacts of the newborn, within hospital constraints.

Provision of Breast Milk

Providing breast milk to newborns may reduce transmission of novel influenza viruses, including pH1N1, to newborns, as breast milk offers many important health benefits including protection against respiratory pathogens.Reference Arifeen, Black, Antelman, Baqui, Caulfield and Becker50Reference Chantry, Howard and Auinger51Reference Howie, Forsyth, Ogston, Clark and Florey52Reference Quigley, Kelly and Sacker53Reference Ip, Chung, Raman, Trikalinos and Lau54Reference Bahl, Frost and Kirkwood55 In fact, the risk of hospitalization for lower respiratory tract disease is more than 250% higher among babies who are fed formula than in those who are exclusively breastfed.Reference Howie, Forsyth, Ogston, Clark and Florey52 Because of the many benefits of breast milk, efforts to provide it to newborns are vital. Depending on the mother's severity of illness and the hospital's configuration and implementation of infection-control procedures, some newborns of mothers with intrapartum pH1N1 infection may be initially separated from their mothers and not fed directly at the breast. Ill mothers who are separated from their infants will need assistance to adequately establish lactation and express and collect their milk. Assistance should be coupled with support and encouragement from hospital staff, and staff should ensure that expressed milk is appropriately handled and stored. When possible, while the newborn is separated from the mother, all feedings should be provided by a healthy caregiver. Breast milk from an infected mother is not considered infectious,Reference Hanson56 and use of antiviral medication by the mother is not a contraindication to breastfeeding.Reference Tanaka, Nakajima, Murashima, Garcia-Bournissen, Koren and Ito57 When the risk of maternal-to-child transmission of infection via respiratory secretions is reduced, the mother should be supported and encouraged to initiate and continue direct breastfeeding. The American Academy of Pediatrics, the World Health Organization, the American College of Obstetricians and Gynecologists, and the US Preventive Services Task Force recommend exclusive breastfeeding for about the first six months of age.5859Reference Gartner, Morton and Lawrence60

Infection Control Practices

Another important strategy to protect newborns from infection with novel influenza viruses, including pH1N1, is implementation of hospital infection-control practices. Newborn exposure to infected secretions can be reduced through adherence to respiratory hygiene and cough etiquette (ie, use of facemasks or tissues to cover nose and mouth when coughing or sneezing), and hand hygiene performed by mothers, family members, health care personnel, and visitors. To improve adherence, facilities should ensure availability of supplies necessary to perform hand and respiratory hygiene as well as cough etiquette.

Implementing isolation/cohorting strategies as well as engineering controls (eg, physical barrier partitions), instituted by hospital policy, is also critical. In the three reports of health care-associated outbreaks of influenza A virus among NICU infants mentioned, cohorting of infected infants in a separate roomReference Munoz, Campbell and Atmar42Reference Sagrera, Ginovart and Raspall43 or separating infected infants from healthy infants using an acrylic wallReference Cunney, Bialachowski, Thornley, Smaill and Pennie41 were important infection-control measures. In the event of maternal infection with pH1N1 during hospitalization for delivery, determining the best option for postpartum and newborn patient management will require careful consideration of the hospital's physical configuration, availability of isolation rooms, and number of patients in need of isolation. Recent trends in design and staffing of labor, delivery, recovery, postpartum, and newborn care units in the United States to accommodate family-centered care may create challenges to isolation of large numbers of ill mothers from their healthy newborns in a pandemic scenario. Therefore, having healthy newborns room with their infected mothers in a postpartum unit may be employed. To reduce transmission risk in this situation, separation of an infected mother from her healthy infant may require modifications to the room (eg, use of a physical barrier, keeping the newborn ≥6 feet from the ill mother). In addition, precautions should be taken to reduce the risk of inadvertent transmission of infection from an ill mother to other unexposed individuals that she might come into contact with during the hospital stay, such as other maternity patients, healthy term infants, and preterm or critically ill newborns in designated newborn nurseries, special care nurseries, or intensive care units.

Other infection-control measures that will provide newborns protection from novel influenza viruses in hospital settings include work restrictions for ill health care personnel and implementing hospital visitor policy restrictions. As ill health care personnel are a potential source of infection to patients, facilities should develop sick leave policies for health care personnel that are nonpunitive, flexible, and consistent with public health guidance to allow and encourage those with suspected or confirmed influenza to stay home. It is also important to ensure that health care personnel, including staff who are not directly employed by the health care facility but who provide essential daily services (eg, environmental cleaning), are aware of sick leave policies. Health care personnel who return to work following illness should be reminded that adherence to hand hygiene, respiratory hygiene, and cough etiquette after returning to work remains important, as viral shedding may occur for several days following an acute respiratory illness. Unnecessary visitors to mothers and newborns during the hospital stay should be limited, and visitors should be screened for symptoms of acute respiratory illness before being allowed to visit the postpartum mother or newborn.

Treatment of Infection

Another strategy to reduce novel influenza infection in newborns is rapid identification of infection and treatment of pregnant women and other close contacts with appropriate antiviral medications (ie, oseltamavir or zanamavir). Studies have shown that treatment with these drugs decreases viral loads and reduces the risk of severe disease and death if started within 48 hours of symptom onset.Reference Louie, Acosta, Jamieson and Honein5Reference Witkop, Duffy and Macias11Reference To, Hung and Li61 Treatment will likely reduce morbidity and mortality even if started more than 48 hours after illness onset, although early treatment is most effective. For pregnant women, early identification of infection and treatment might also benefit the unborn fetus by preventing preterm delivery as a consequence of severe maternal illness. With respect to newborns themselves, although emergency use of oseltamivir, as clinically indicated, was authorized by the FDA for term infants younger than age one year for pH1N1 treatment during the pandemic,17 data are limited on the safety and dosing of oseltamivir for this age group and offer no specific guidance for use among preterm infants (<37 weeks' gestation or corrected postmenstrual age). Moreover, chemoprophylaxis with oseltamivir is not recommended in infants younger than three months of age, unless the exposure is significant and the infant is considered at high risk of severe illness.17