**3. TORCH infections**

*Congenital Anomalies in Newborn Infants - Clinical and Etiopathological Perspectives*

been developed to replace the prior diagnosis of chorioamnionitis [7]. IAI was updated in 2017 by the American College of Obstetricians and Gynecologists into three categories which are readily diagnosed. Isolated maternal fever (IMF) is the first category, in which the mother has a single intrapartum temperature of ≥39.0°C or a temperature of 38.0–38.9°C that persists for 30 min, with treatment recommendations including the consideration of broad-spectrum antibiotics [7, 8]. Given the numerous potential causes of maternal fever, the utilization of antibiotics is at the providers' discretion. Suspected IAI is diagnosed when the mother has an elevated temperature (≥39.0°C) or a slightly elevated temperature (38.0–38.9°C) along with one of the following risk factors: maternal leukocytosis, purulent cervical drainage or fetal tachycardia [7, 8]. Confirmed IAI is diagnosed with a positive amniotic fluid test or placental pathology demonstrating histologic evidence of infection [7]. Similar to the previously used histological chorioamnionitis, a criticism of this diagnosis is that it is made after the clinical situation has resolved, and thus does not aid in the acute management of the mother or the infant. Both suspected and confirmed IAI diagnoses should result in treat-

ment with intrapartum antibiotics and antipyretics [7].

IAI is present in nearly 50% of very early preterm birth [9], after which multiple complications can occur and a wide array of neonatal morbidities and mortalities are observed. This has led to speculation that IAI is directly impacting the fetal and neonatal development and outcomes, as well as potentially resulting in preterm birth, which then impacts development and outcomes. The majority of studies that have investigated this question utilized diagnoses of chorioamnionitis, which included both clinical and histological cases. Given the variation of diagnoses included in these studies, it is not surprising that the results have also been varied. A large study of 2390 extremely preterm infants (born <27 weeks' gestational age) from sixteen centers across the United States found infants exposed to histological and clinical chorioamnionitis had an increased risk of cognitive impairment at 18–22 months' corrected age [10]. A separate study of 350 infants found that while gestational age was significantly lower among those with exposure to histological chorioamnionitis, there was no association with intraventricular hemorrhage, white matter injury around birth, or differences in cognitive or motor outcomes at 18–24 months' corrected age [11]. Additional studies have found weak causal or associative roles of chorioamnionitis with cerebral palsy risk [12] and no increased risk of white matter injury on magnetic resonance imaging (MRI) following histological chorioamnionitis in premature infants [13]. Additional investigation is required with the new IAI definitions to determine if there are consistent findings with developmental outcomes in those

Chorioamnionitis is the term that has been used for decades to describe infection and/or inflammation of the chorion, amnion, or both. This has been further delineated into a "clinical" diagnosis based on maternal symptoms, and a "histological" diagnosis based on the pathology of the placenta following delivery. Clinical signs and symptoms are used to diagnose clinical chorioamnionitis, and include maternal fever, uterine fundal tenderness, maternal and/or fetal tachycardia and purulent amniotic fluid [5]. The most common bacterial organisms to cause chorioamnionitis are *Ureaplasma urealyticum* and *Mycoplasma hominis*. Histological chorioamnionitis is diagnosed by observing neutrophil infiltration into the chorion and amnion [6]. The variation in the definition of chorioamnionitis has resulted in confusion in neonatal management as well as difficulty in assessing the long-term impact of chorioamnionitis on development. Therefore, intra-amniotic infection (IAI) has

**2. Chorioamnionitis/intra-amniotic infection (IAI)**

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diagnosed with IAI.

TORCH infection is a mnemonic that has classically been used to describe congenital infections that can impact fetal development. In the past, TORCH represented Toxoplasmosis, Other (syphilis, varicella-zoster, parvovirus B19 and newer pathogens such as Zika), Rubella, Cytomegalovirus and Herpes Simplex Virus. However, as more pathogens are being discovered and the "other" category is expanding, some experts feel the mnemonic is not as relevant today.
