W.J. Yang, et al ■ SHORT COMMUNICATION ■

FETAL ASSOCIATED WITH PRENATAL METHAMPHETAMINE EXPOSURE

Wen-Jui Yang1, Chie-Pein Chen1,2*, Chen-Yu Chen1, Kuo-Gon Wang1, Tsung-Hsien Su1,2 1Department of Obstetrics and Gynecology, Mackay Memorial Hospital, and 2Mackay Medicine, Nursing and Management College, Taipei, Taiwan.

SUMMARY Objective: In roughly 50% of all patients with meconium peritonitis, there is no evidence of primary obstruction of the bowel. We report a case of maternal methamphetamine and heroin abuse complicated by fetal meconium pseudocyst without a definite intestinal obstructive lesion. We discuss the correlation between the presence of meconium peritonitis and prenatal exposure to methamphetamine. Case Report: A 19-year-old, gravida 2, para 0, abortus 1, woman had abused illegal drugs, including methamphetamine and intravenous heroin. Suffering from withdrawal symptoms, she was taken to a shelter where she was diagnosed with a of 26 weeks’ gestation. The patient underwent cesarean section at 34 weeks due to preterm labor and fetal malpresentation. A boy weighing 2,474 g was born, but had to be intubated and admitted to the intensive care unit because of a distended abdomen and respiratory distress. A laparotomy performed on the second day of life revealed a large calcified pseudocyst associated with two perforations of the distal jejunum. A segmental resection of the jejunum with primary anastomosis was performed. The infant recovered well after the operation and was discharged 65 days after birth. Conclusion: Since methamphetamine is a powerful _-adrenergic stimulant and induces the release of catecholamines from adrenergic synapses, it can cause powerful vessel constriction. Prenatal exposure to methamphetamine can cause disruption of mesenteric blood flow with transmural necrosis of the bowel, resulting in bowel perforation and meconium peritonitis. [Taiwanese J Obstet Gynecol 2005;44(2):180–182]

Key Words: meconium peritonitis, methamphetamine

Introduction not totally sealed, a thick-walled cystic cavity forms, and meconium will continue to enter this cystic space. The Meconium peritonitis is defined as a sterile reaction in meconium cyst may entrap or compress the surrounding the fetal abdomen resulting from intrauterine bowel intestines [2,3]. The association of meconium peritonitis perforation. It occurs in one in every 35,000 live births with maternal prenatal cocaine abuse has been reported [1]. The intense inflammatory reaction forms a dense, in the literature, with the authors attributing it to the adherent membrane that effectively seals off the intestine vascular effects of cocaine [4]. Amphetamines, a group at the site of perforation. If, however, the perforation is of sympathomimetic drugs, have pharmacologic ef- fects similar to cocaine. Members of this group include amphetamine, dextroamphetamine and methamphet- amine. They are powerful _-adrenergic stimulants and induce the release of catecholamines from adrenergic *Correspondence to: Dr. Chie-Pein Chen, Division of High Risk Pregnancy, Department of Obstetrics and Gynecology, Mackay synapses [5]. Memorial Hospital, 92, Section 2, Chung-Shan North Road, Here, we report a case of meconium pseudocyst in a Taipei 106, Taiwan. baby whose mother abused methamphetamine and E-mail: [email protected] heroin during pregnancy. The possible relationship Received: October 21, 2004 Revised: November 8, 2004 between drug effects and meconium peritonitis is Accepted: November 9, 2004 discussed.

180 Taiwanese J Obstet Gynecol • June 2005 • Vol 44 • No 2 Meconium Peritonitis & Methamphetamine

Case Report obstructive lesion can be demonstrated, the most common being volvulus, atresia, intussusception, A 19-year-old, gravida 2, para 0, abortus 1, woman had vascular insufficiency, duplication, stenosis, congenital abused illegal drugs, including methamphetamine (by bands, , meconium plugs, imperforate inhalation for 6–7 years) and heroin (injected intra- anus, Meckel’s diverticulum, hyperplastic lymphoid venously in the previous 6 months). Suffering from tissue and colonic aganglionosis [2,7]. In addition, withdrawal symptoms, she was taken to a shelter where bowel ischemia secondary to prenatal anoxic events she was diagnosed with a pregnancy of 26 weeks’ may cause perforation with subsequent meconium gestation. She presented for prenatal care at 28 weeks; peritonitis [8,9]. ultrasound showed a fetus with biometric data appro- Lloyd suggested that intestinal perforation is priate for gestational age. However, polyhydramnios associated with diminished mesenteric blood flow due and fetal ascites with a large echogenic cyst (7.23 = to [10]. Tibboel et al hypothesized 3.26 cm) in the left upper abdominal cavity were present that a temporary reduction in mesenteric blood flow (Figure). Amniocentesis revealed a 46XY karyotype. The may lead to necrosis of the mucosa, which may in turn mother’s urinary methamphetamine concentration was cause complete obstruction of the intestinal lumen, 788 ng/mL, with opiate metabolites of 448 ng/mL. resulting in atresia of the small bowel [11]. Persistent The patient underwent cesarean section at 34 weeks reduction of mesenteric blood flow can lead to due to preterm labor and fetal malpresentation. A boy transmural bowel necrosis. Depending on the rate of weighing 2,474 g was born, with Apgar scores of 5 and this process, perforation may occur, resulting in 9 at 1 and 5 minutes, respectively. The baby was intu- meconium peritonitis without [11]. bated and admitted to the intensive care unit because Amphetamine is a phenylisopropylamine and is of a distended abdomen and respiratory distress. A structurally similar to endogenous catecholamines laparotomy performed on the second day of life revealed and neurotransmitters. It is a powerful _-adrenergic a large calcified pseudocyst associated with two per- stimulant that induces the release of catecholamines forations of the distal jejunum. A segmental resection of from adrenergic synapses, which are then primarily the jejunum with primary anastomosis was performed. responsible for the peripheral actions of the drug. Ma- The infant recovered well after the operation and was ternal use of amphetamines during pregnancy carries a discharged 65 days after birth. significant risk of intrauterine growth retardation and premature delivery [12]. Methamphetamine is very similar to amphetamine, but has a higher ratio of Discussion central to peripheral effects [5]. In near-term pregnant sheep given intravenous amphetamine at or below Meconium peritonitis is the result of an intrauterine commonly used recreational doses, methamphetamine perforation of the small bowel or, rarely, other sites of rapidly crossed the placenta and accumulated in the the [2,3]. It may occur as early as fetus [13,14]. Fetal ovine blood pressure increased 20– 24 weeks of gestation [6]. In 50% of cases, a definite 37% with a decrease in fetal oxyhemoglobin saturation and arterial pH. Methamphetamine has pharmacologic effects similar to cocaine, including vasoconstriction and infarction [15]. Cocaine, a potent vasoconstrictor, is strongly suspected to be a teratogen. Maternal cocaine administration may impose notorious effects on the developing fetus via cocaine-induced maternal uterine hypoperfusion and hypoxemia [16], and direct cocaine- mediated vasospasm, hypertension, and tachycardia with subsequent microregional infarction [17]. This could lead to loss of an existing structure, or stricture of that structure; utero-intracranial vascular accidents, transverse limb defects, and necrotizing enterocolitis following cocaine exposure support such a mechanism [4,18,19]. Figure. Ultrasound of the fetus (transverse abdomen) at 28 Fetuses exposed to cocaine have exhibited various weeks of gestation shows the presence of fetal ascites (thin disruptive pathogenic vascular anomalies, including arrow) and a large echogenic cyst (thick arrow). complex choroid cysts, gastroschisis, meconium peri-

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