What We Have Learned Regarding Antibiotic Therapy for the Reduction of Infant Morbidity After Preterm Premature Rupture of the Membranes Brian M. Mercer*, Robert L. Goldenberg†, Anita F. Das‡, Gary R. Thurnau§, Robert W. Bendon¶, Menachem Miodovnik, Risa D. Ramsey**, and Yolanda A. Rabello†† for the National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network Preterm premature rupture of the membranes (pPROM) is responsible for approximately one third of the over 450,000 preterm births occurring in the United States annually. In this manuscript, we summarize the outcomes and analyses related to the National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network (NICHD-MFMU) network multicenter trial of antibiotics to reduce infant morbidity after pPROM. Based on evident reduction in gestational age dependent and infectious infant morbidity, we provide the rationale for aggressive intravenous and oral, broad spectrum Ampicillin/Amoxicillin, and Erythromycin therapy during conservative man- agement of pPROM before 32 weeks’ gestation. We further review the histopathologic correlates to pPROM, to antibiotic treatment, and to perinatal outcome, and discuss the relationships between maternal and neonatal cytokine levels intercellular adhesion molecule, and other clinical and plasma markers regarding perinatal morbidity. The use and limitations of ultrasound and vaginally collected amniotic fluid pulmonary maturity assessment are discussed. © 2003 Elsevier Inc. All rights reserved. Preterm premature rupture of the membranes (pPROM) is responsible for approximately one third of the over 450,000 preterm births occurring in the United States annually. 1 Preterm PROM is associated with brief latency to delivery, maternal and neonatal infection, and umbilical cord com- pression due to oligohydramnios. Even with con- servative management, the majority (70%-80%) of women with pPROM remote from term will de- liver within 1 week of membrane rupture, placing the infant at risk for complications of immaturity in addition to those specifically related to prema- ture membrane rupture. Delivery before 32 weeks’ gestation is associ- ated with a significant risk of neonatal compli- cations, including severe acute morbidity and death. Because of this, the stable gravida with pPROM remote from term is generally best served by conservative management in an at- tempt to prolong pregnancy and reduce the risk of gestational age dependent morbidity in the newborn. Despite conservative efforts, many women will ultimately deliver after a brief la- tency. However, a subset of these women will remain pregnant for an extended period of time, allowing their fetus to mature in utero. Offsetting this potential benefit is the risk for development of amnionitis and fetal infection, abruptio placentae, and umbilical cord compres- sion due to oligohydramnios. From the Departments of Obstetrics and Gynecology, *Case Western Reserve University, Cleveland, OH, †University of Alabama, Bir- mingham, AL, ‡Biostatistical Coordinating Center of George Wash- ington University, Washington, DC, §St. John’s Regional Health Center, Springfield, MO, ¶Department of Pathology, of Korsair’s Children’s Hospital, Louisville, KY, Columbia University, New York, NY, **University of Tennessee, Memphis, TN, and the ††White Memorial Medical Center, Los Angeles, CA. This work supported by grants U10-HD-21434, U10-HD-27917, U10-HD-27915, U10-HD-27869, U10-HD-27905, U10-HD- 27861, U10-HD-27860, U10-HD-27889, U10-HD-27883, U10- HD-21414, and U10-HD-19897 from the NICHD, and MO1-RR- 000080 of NCRR. Reprints are not available. © 2003 Elsevier Inc. All rights reserved. 0146-0005/03/2703-0006$30.00/0 doi:10.1016/S0146-0005(03)00016-8 217 Seminars in Perinatology, Vol 27, No 3 (June), 2003: pp 217-230