Neonatal Uterine Bleeding in a 6-Day-Old Neonate

A 31-year-old gravida 4, para 2-1-0-3 sought prenatal care in our facility after she got incarcerated in her third trimester. Her due date is based on her last menstrual period, which is confirmed at our institution with third-trimester ultrasonography. She presents to the hospital at 38 weeks and 3 days to rule out labor. She is admitted for prelabor rupture of membranes (PROM) with thick meconium. Her labor course is unremarkable, and she delivers a viable female neonate with Apgar scores of 8 and 9 at 1 and 5 minutes and a birthweight of 2,790 g.Previous prenatal records are unavailable; however, she claims that her prenatal course was uncomplicated. Her medical history is significant for methamphetamine, cocaine, heroin, and marijuana use. Her prenatal laboratory findings are significant for a reactive hepatitis C antibody with an undetectable viral load. The patient’s urine drug test is negative. During her incarceration, she is started on nightly sertraline for the treatment of depression.The neonate was admitted to the NICU because of respiratory distress and was placed on oxygen. An evaluation to rule out sepsis was initiated for concern of pneumonitis versus bronchitis, and the neonate was started on ampicillin and gentamicin for 2 days.On day 6 after birth, the neonate developed bright red vaginal bleeding, which was noticed during regular diaper change (Fig). On physical examination, the external genitalia had no lesions, with normal labia majora and minora. Upon spreading the labia, the vaginal canal was noted to be pink and moist with bright red blood present. Gentle palpation of the genitalia and lower abdomen did not aggravate the neonate. Although the bleeding started with multiple daily bright red episodes, it became a dark red discharge on day 8 and then a scant discharge on day 9, after which it subsided.Findings of complete blood cell count and complete metabolic panel remained within normal limits. A coagulation evaluation was performed, which showed normal prothrombin time (12.6 s), international normalized ratio (1.0), and activated partial thromboplastin time (28.8 s). Her Coombs test result was negative. She remained asymptomatic throughout the hospitalization: she fed without vomiting and had an appropriate number of nonbloody voids and stools. The neonate was weaned off high-flow nasal cannula oxygen over 11 days and was then stable for discharge from the hospital.Upon investigation, the mother denied recent exposure to progesterone products, barbiturates, or aspirin, or any family history of bleeding disorders. She did, however, note that her older daughter had a similar bleeding episode in her first week after birth that was worrisome and subsided after a week.Neonatal progesterone drop after birthClassic vitamin K deficiencyPrenatal exposure to anticoagulants (aspirin) or antiepileptics (barbiturates)Neonatal uterine bleeding (NUB) has been documented to occur in female neonates on days 3 to 5 after birth, with a prevalence of 3% to 5% for overt NUB and 25% to 60% for occult NUB. (1) NUB has been associated with intrauterine fetal distress. Low birthweight, preeclampsia, postmaturity, and fetomaternal blood incompatibility have been reported to be significantly associated with its occurrence. (2) Our case, however, does not match these associations. Nonetheless, because of the PROM with thick meconium, it can be suggested that the fetus was under distress.A proposed etiology of NUB is the rapid drop in progesterone after delivery, causing interstitial bleeding during the first week after birth. Although the uteri of most female fetuses are resistant to the effects of progesterone, Ober and Bernstein (3) observed endometrial histologic findings consistent with secretory changes in 5% of term neonates. According to Brosens et al, (1) this indicates that this population underwent fetal uterine decidualization during the third trimester in response to maternal progesterone and is not resistant to its effect. After delivery and upon progesterone withdrawal, the neonate will undergo bleeding resembling that of a menstrual cycle as the shedding occurs. However, currently, no evidence has confirmed this explanation.Classic vitamin K deficiency could also be an etiology for NUB within the first week after birth. In this case, NUB could present in addition to mucocutaneous bruising in mild cases or intracranial hemorrhage in severe ones. This type of bleeding can be caused with the use of anticoagulants, antiepileptics, or certain antibiotics during pregnancy. (4) To evaluate this etiology, a coagulation panel can be performed to evaluate the degree of the deficiency, and vitamin K can be administered accordingly. Given that our patient’s laboratory findings were within normal limits, a coagulation abnormality was ruled out, and a diagnosis of NUB was made.When NUB is noted, providers describe the proposed etiologies to the parents and assume, based on previous occurrences in the literature, that its presence is physiologic. General assumptions for the length, frequency, and anticipated course of such bleeding are explained to the parents. However, no definitive criteria have been suggested for a pathologic NUB that might require additional investigation versus a physiologic one. For instance, some NUB episodes have been described as blood-tinged, whereas other episodes were presented as grossly bloody. (5) In our case, the newborn had bright red bloody discharge several times a day. Although our patient’s NUB ended within a few days, we were uncertain if this NUB was physiologic or pathologic, as its presentation was alarming and, unlike previous episodes of NUB encountered by our clinicians or occurrences described in the literature. We found that no standards have been established to recommend necessary investigations in cases of NUB where the presentation is unlike what has been described in the literature or what a seasoned physician would consider typical.Encountering this case highlighted the scarcity of criteria and guidelines available to investigate the specific etiology of NUB, identify any potential pathology, and advise parents on how to proceed when such episodes are encountered. This might be due to low reporting of such incidents and, consequently, even fewer studies performed on the matter. The neonate in this case was weaned off high-flow nasal cannula oxygen over 11 days and was then stable for discharge from the hospital.Although NUB episodes usually resolve within a few days, recording them is necessary to identify the prevalence of their occurrence in different populations, recognize general associations, establish a confirmed etiology, and provide timely and accurate information to parents, for which such episodes can be very worrisome. Another reason to record such episodes is the link between NUB and future gynecologic pathology. Recent data have highlighted a hypothesis linking NUB with endometriosis. It is suggested that endometrial stem cells are extrapolated during NUB and may disseminate in the pelvis and can thus be responsible for early-onset endometriosis. (6) Recording such events might later aid clinicians in diagnosing endometriosis in unlikely presentations and starting treatment earlier.To report cases of NUB, the International Classifications of Diseases (ICD) code for neonatal vaginal hemorrhage can be used (ICD-10-CM). It is defined as neonatal pseudomenses. Because many presentations of NUB can be illustrated under that code, it is vital to document the presentation in detail. It is worth mentioning that there is no ICD code to record mothers of patients with NUB. Once documented, a pattern for NUB presentation can be suggested through retrospective studies, and the etiology of such events can be investigated.The progesterone withdrawal hypothesis outlined earlier can be explored by obtaining the progesterone level on day 1 after birth and following the trend of that level. Moreover, abdominal ultrasonography showing the decidualization and endometrial thickness in female neonates could help confirm Ober and Bernstein’s aforementioned observations. (3) Specifically, these investigations can be performed in patients who have a higher association with NUB secondary to fetal distress. In addition, an older female sibling who has a history of NUB should trigger such investigations in the current female neonate as they might be at an elevated risk of developing NUB. That said, a genetic association can also be examined.There is a lack of standards for defining physiologic NUB episodes and a lack of guidelines to investigate a potential pathology.There is a need to record NUB episodes as it would provide a framework for understanding these occurrences, guiding parents accurately, and even aiding in future endometriosis diagnoses.After thorough documentation of these episodes in concordance with laboratory investigations and pelvic imaging, attention can be turned to establishing a definition for a typical presentation, a definitive etiology, and future avenues to explore.American Board of Pediatrics Neonatal-Perinatal Content SpecificationsKnow the effects of maternal thromboembolic or potential thromboembolic (eg, artificial valve) disorders and their management, including the use of anticoagulants, on the fetus and/or newborn infantKnow the definition, risks to the fetus and/or newborn infant, and management of postterm pregnancyKnow the effects of mild preeclampsia on the fetus and/or newborn infant and its managementKnow the diagnostic evaluation and perinatal management of fetal-maternal blood group incompatibility