The Impact of Infection During Pregnancy on the Mother and Baby
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16 The Impact of Infection During Pregnancy on the Mother and Baby Heather E. Jeffery and Monica M. Lahra Infection continues to account for a major pro- ascending infection from the lower genital tract, portion of maternal, fetal, and neonatal mortality and perinatal acquisition, which includes nos- and morbidity worldwide. ocomial infection and transmission of infection In the developing world, maternal systemic via breast milk (maternal or banked milk). infections, such as pneumonia, malaria, tubercu- The impact of infection (bacterial, viral, or losis, typhoid fever, and pyelonephritis, which are other) on the mother or the fetus is dependent often functions of poverty, crowding, and malnu- on maternal and fetal factors in addition to the trition, impose health costs to the mother and pathogenic properties of the infecting agent. risks to the fetus. These risks include spontaneous Maternal factors include immune function and abortion, stillbirth, preterm labor and preterm status, anatomical factors, and comorbidity. birth, low birth weight, intrauterine growth Infecting agent factors include dose, exposure, restriction (IUGR), and infection. This is in addi- and individual virulence factors. Fetal factors tion to the rapidly escalating rates of a number of include gestational age, developmental stage, and sexually transmitted diseases, in particular, fetal immune function. Table 16.1 summarizes human immunodefi ciency virus (HIV) infection the potential impact on the fetus and neonate with its associated comorbidities. with respect to the ante-, peri-, and postnatal In the developed world, preterm birth remains periods. a major, unresolved public health issue. Intrauter- The impact of infection in pregnancy on both ine infection has been shown to play a major role mother and baby is discussed in this chapter. in induction of preterm birth and neonatal infec- tion (Goldenberg et al. 2000b). More recently the contribution of asymptomatic bacteruria (Rouse Infection and Preterm Birth et al. 1995; Smaill 2001), periodontal disease (Offenbacher et al. 1996; Newnham et al. 2005), Preterm birth is the leading cause of perinatal and abnormal vaginal fl ora (Kiss et al. 2004) to death and long-term handicap, accounting for preterm labor and delivery has been recognized. 70% of perinatal deaths in developed countries such as the United States, where approximately 10% of all births are preterm (Goldenberg et al. Congenital Infections 2000b). Preterm births can be categorized into three Vertical transmission of infection (from mother groups (Arias and Tomich 1982): (1) spontaneous to baby) occurs across mammalian species preterm labor and intact membranes; (2) preterm causing injury, malformation, sepsis, and death. labor with prelabor rupture of membranes; and The mode of transmission of infection from (3) preterm birth indicated for maternal or fetal mother to fetus includes the hematogenous route, reasons. Preterm deliveries that fall into the fi rst 379 380 H.E. Jeffery and M.M. Lahra TABLE 16.1. Impact of congenital infection on pregnancy infection (e.g., listeriosis). Uncommonly, retro- outcome grade infection via the fallopian tubes or Antenatal Perinatal Postnatal iatrogenic infection introduced from invasive Preterm labor Sepsis Infection procedures such as amniocentesis occurs Fetal injury Perinatal death Malformation (Goldenberg et al. 2000b) (Fig. 16.1). Malformation Developmental Ascending infection resulting in chorioamnio- Intrauterine growth abnormalities nitis may account for up to 50% of preterm restriction Small for gestational age births at less than 30 weeks’ gestation (Lockwood Intrauterine death Neonatal death 2002). The organisms implicated are largely anaerobes and genital mycoplasmas, but can two categories are most commonly associated include organisms such as group B streptococcus with ascending intrauterine infection. (GBS). The source of intrauterine infection is most The infl ammatory response in chorioamnion- commonly ascending organisms from the lower itis is predominantly maternal in origin. Chorio- genital tract and less commonly blood-borne amnionitis may be diagnosed by histological or FIGURE 16.1. Cross section of a gravid uterus illustrating routes of intrauterine infection. (From Goldenberg et al. 2000b, with permission. Copyright © 2000, Massachusetts Medical Society. All rights reserved.) 16. The Impact of Infection During Pregnancy on the Mother and Baby 381 70 n = 261 n = 200 60 n = 139 n = 164 50 40 n = 236 n = 284 n = 375 n = 380 30 n = 539 n = 580 Histological chorioamnionitis % 20 n = 770 10 n = 6139 0 20–24 25 26 27 28 29 30 31 32 33 34 37–40 Gestational Age (completed weeks) FIGURE 16.2. Incidence of histological chorioamnionitis by gestational age in a large preterm cohort compared with a term cohort. (From Lahra and Jeffery 2004, with permission from Elsevier.) by clinical fi ndings. The hallmarks of clinical rupture (preterm prelabor rupture of membranes) chorioamnionitis are maternal fever, uterine and cervical maturation leading to preterm birth tenderness, and discharge. However, it is (Romero et al. 2003). im portant to note that in the vast majority of Entry of organisms or bacterial products into cases chorioamnionitis is clinically silent and is the amniotic fl uid and subsequently into the fetus most often diagnosed histologically. There is a similarly provokes elevated fetal proinfl amma- linear and inverse relationship between histo- tory cytokine levels in a response known as the logical chorioamnionitis and gestational age, fetal infl ammatory response syndrome (FIRS). and it is most common at gestations less Subclinical fetal infection is underrecognized and than 30 weeks (Lahra and Jeffery 2004) (Fig. is associated with preterm birth, fetal injury, and 16.2). The incidence of histological chorio- intrauterine death. It is also associated with infec- amnionitis at term gestation, using the same tion in the neonatal period. One study found that methodology and diagnostic criteria, was 3.8% fetal bacteremia was eight times more likely in (Russell 1979). women with positive amniotic fl uid cultures than The infl ammatory response includes the pro- those with negative cultures (33% versus 4%) duction of proinfl ammatory cytokines and infl am- (Carrol et al. 1996). matory mediators (prostaglandins, leukotrienes, The fetal infl ammatory response is manifested etc.). The associative evidence suggests that histologically as chorionic vasculitis, umbilical infl ammation triggers prostaglandin synthesis in vasculitis, or funisitis (Yoon et al. 2000; Pacora the amnion, chorion, decidua, and myometrium, et al. 2002). leading to myometrial contractions and cervical The fetal infl ammatory response and its impor- dilatation (preterm labor) with further augmenta- tance has been summarized by Leviton et al. tion of the whole process. Proinfl ammatory cyto- (1999): kines also stimulate production of matrix metalloproteases by the chorion and amnion, • The fetus contributes to the cellular infl amma- which lead to cervical ripening and membrane tory response in amniotic fl uid infection. 382 H.E. Jeffery and M.M. Lahra • The more severe the histological infl ammatory These fi ndings highlight the importance of response, the higher the level of cytokines in the histological and microbiological examination of amniotic fl uid. the placenta, extraplacental membranes, and • Funisitis is better than membrane infl amma- umbilical cord in preterm birth, stillbirth, and tion in predicting preterm labor and perinatal term babies requiring admission to an intensive death. care facility. The role of cytokine measurement in • Elevated proinfl ammatory cytokine levels in the clinical practice and prediction of preterm labor amniotic fl uid, umbilical cord blood, and early is in evolution. neonatal blood are some of the best predictors of preterm parturition, cerebral white matter damage, and cerebral palsy. Specific Maternal Infections • Proinfl ammatory cytokines are elevated in the brains of infants who die with histological evi- Urinary Tract Infection dence of white matter damage. Background Chronic Uterine Infection Urinary tract infections (UTIs) are the most common bacterial infection in pregnancy and While intrauterine infection has been considered occur when bacteria enter and infect the normally to be acute, there is evidence suggesting that sterile urinary tract. Urinary tract infection may it may be chronic. Genetic amniocentesis at 16 be classifi ed as symptomatic bacteruria and to 21 weeks identifi ed Mycoplasma hominis and asymptomatic bacteruria. Ureaplasma urealyticum on culture in a small Symptomatic infections may be localized to number of women (Cassell et al. 1983). This the bladder (cystitis) or involve kidney infection clinically silent infection was associated with (pyelonephritis) with systemic symptoms and adverse pregnancy outcome (pregnancy loss and signs. Urinary tract anomalies, HIV, and diabetes preterm birth) and histological chorioamnion- increase the risk of pyelonephritis as does preg- itis. Similarly, in summarizing cytokine fi ndings nancy (Foxman 2003). in midtrimester amniotic fl uid, Romero et al. By contrast, asymptomatic bacteruria (ASB) is (2003) reported higher median interleukin-6 (IL- more common and requires screening midstream 6) levels in amniotic fl uid of those who delivered urine at the fi rst antenatal visit for detection, pref- preterm compared to those who delivered at erably at 12 to 16 weeks’ gestation (Nicolle et al. term. Maternal IL-6 levels were not associated 2005).