Case Reports

Indian Pediatrics 2002; 39:385-388  

Massive Fetomaternal Hemorrhage with Persistent Pulmonary Hypertension in a Neonate

From the Department of Neonatology, Kirwan Hospital for Women Townsville, Queensland 4817, Australia.

Correspondence to: Dr Sanjay Patole, Department of Neonatology, Kirwan Hospital for Women Townsville, Queensland 4817, Australia.

E-mail: [email protected]

Manuscript received: July 4, 2001;

Initial review completed: August 30, 2001;

Revision accepted: September 11, 2001.

Massive fetomaternal hemorrhage (FMH) is defined as loss of over 150 ml of blood; its frequency is largely unknown(1). It has been reported as an unexpected cause of death in 13.8% of otherwise unexplained fetal deaths(2). Association of persistent pulmonary hypertension of the newborn (PPHN) with severe anemia following massive FMH is known but not well documented(3,4). We report such an association in a term neonate needing rescue therapy with high-frequency oscillatory ventilation (HFOV) and inhaled nitric oxide (INO).

A 39-year-old mother (gravida-9, para-1, miscarriages-4, ectopic pregnancies-2, term-ination of pregnancy-1). delivered a female neonate weighing 3.3 kg at term following an emergency Caesarean section due to decreased fetal movements with sinusoidal pattern on the non-stress test. A CTG done for decreased fetal movements 2 weeks prior to the delivery was normal. Follow up CTG/biophysical profile, and ultrasonography could not be done due to patient noncompliance. There was no history of trauma, vaginal bleeding, diabetes mellitus, urinary tract infection, or use of non-steroidal anti-inflammatory drugs like indomethacin. At birth, the baby was hydropic, very pale, floppy with weak peripheral pulses, and had a heart rate of 70/minute. Apgar scores were 1 and 5 at 1 and 5 minutes, respectively. The cord pH and Hb were 7.08 and 2.5 g/dl, respectively. She was resuscitated using intermittent positive pressure ventilation after endotracheal intubation, intra-tracheal adre-naline, and transfusion of 120 ml of group O-negative packed red cells immediately over 2 hours followed by 44 ml of cross matched red cells over 2 hours followed by a single dose of furosemide. The baby’s post transfusion hemoglobin was 14.6 g/dl (hematocrit = 0.43) at 14 hours of age. The direct Coombs test was negative. Maternal Kliehauer Betke test was positive. (Estimated fetomaternal bleed: 154 ml). The placental histopathology was normal. Maternal Parvovirus B19 IgM was non-reactive. Specific IgM titers for toxoplasmosis, rubella, cytomegalovirus, and herpes simplex I and II were negative. The relevant laboratory investigations were as follows: Nucleated RBC’S 542/100 WBC, WBC count 10000/mm3, Platelet count - 57000/mm3, blood culture - negative, serum creatinine-0.13 mmo1/L, serum bilirubin - 60 mmo1/L, total proteins - 3.2 g/L, albumin - 1.4 g/L, AST - 141 IU/L, ALT 42 IU/L, GGT - 21 IU/L, cranial ultrasound - normal.

Sonography revealed severe ascites with no evidence of pleural/pericardial effusions. Color Doppler study showed a structurally normal heart with evidence of PPHN (tricuspid regurgitation, right to left flow across the patent ductus arteriosus). Addi-tionally, the difference between pre and post ductal saturations by pulse oximetry was > 15%. HFOV (MAP = 17 cm H2O, amplitude = 59) was resorted to at 5 hours of age in view of the rising ventilatory requirements (PIP/PEEP - 35/6 cmH2O, rate - 55/minute) and unstable oxygenation (PO2 - 24-204 mmHg) in 100% oxygen along with surfactant therapy, sedation, muscle paralysis, inotrope therapy. INO was subsequently started at 6 hours of age (oxygenation index - 62) at 20 ppm and later increased to 30 ppm. Following a sustained improvement in oxygenation commencing at 7 hours of age, the inspired oxygen con-centration was reduced to 40% by 60 hours of age and the mean airway pressure was weaned to 8 cm H2O by 75 hours of age. Cardiovascular stability allowed inotropes (dopamine, dobutamine) to be weaned off by day 3. INO was subsequently weaned off by day 4 and the neonate was extubated to room air on day 6. The urine output had increased to 8-9 ml/kg/hour by day 5 with significant resolution of the generalized edema by day 7. Further hospital stay was uneventful and the neonate was neurologically normal at discharge on day 12.

FMH of over 30 ml of fetal blood occurs in normal pregnancies with a frequency of about 1 in 300(1). Defined as the loss of more than 150 ml (or approximately 50% of the fetal blood volume), massive FMH is rarely suspected before fetal death(5,6).

PPHN has been reported as a consequence of massive FMH (3,4). Frickers et al. reported massive FMH leading to marked anemia (Hb - 4.9 g/dl) and rapidly progressive heart failure in a neonate who developed symptoms of ‘persistent fetal circulation’ (PFC) despite blood transfusion and digoxin therapy but survived(3). Moya et al reported 4 cases of massive FMH presenting with severe anemia (hematocrit - 16-26%) and signs of circulatory failure(4). One of these neonates with pallor (Hb - 5.5 g/dl), weak peripheral pulses, systemic hypotension, soft systolic murmur and hepatomegaly deteriorated rapidly, developing PPHN documented on echocardiography. Though the mother had gestational diabetes, echocardiography of this neonate did not reveal poor cardiac contract-ility or cardiomyopathy that is usually seen in infants of diabetic mothers. Red cell trans-fusion and mechanical ventilation with 100% oxygen were required to stabilize the neonate. At discharge the neonate was neurologically normal.

The factors associated with the patho-genesis of PPHN include acute as well as chronic hypoxia(7,8). It is well documented that acute hypoxia causes smooth muscle contraction in pulmonary arteries through a direct effect on intracellular calcium levels(8). The mechanisms of pulmonary endothelial adaptation to sustained hypoxia include reduction in nitric oxide production, possibly through reduced activity of formative enzyme nitric oxide synthase that may enhance the development of secondary pulmonary hyper-tension(8). Cardiac output and hemoglobin are the key elements in determining systemic oxygen transport(9). Additionally hypovole-mic, anemic hypoxia (e.g., hemorrhagic shock) is less well tolerated compared to hypoxic hypoxia(9). Given this evidence, prompt correction of anemia/hypovolemia and aggressive prevention (e.g., management of hypoglycemia, hypothermia) and management of PPHN is warranted in cases of FMH(7,9,10).

Contributors: VP performed the literature search and prepared the initial draft of the manuscript. SKP and JSW helped in final drafting of the manuscript. SKP will act as the guarantor for the manuscript.

Funding: None.

Competing interests: None stated.

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