A total of 4 of 153 low birth weight infants at our hospital were found to have pseudo-Bartter syndrome in 2005 and 2006. The neonates (two of whom were twins; light for gestational age 2, appropriate for gestational age 1 and small for gestational age 1) showed symptoms of apnea and/or poor feeding or patent ductus arteriosus, which disappeared by day 4. Hypokalemia, hypochloremia and metabolic alkalosis normalized by day 8. The mothers had repeatedly rushed to the restroom after eating while in hospital, and were lighter at delivery than before pregnancy; however, vomiting was not observed. The mothers had several stress factors related to pregnancy, and all recovered from the eating disorder after delivery. Urinary Cl/creatinine (mequiv. mg−1) and serum Mg in the infants were <0.1 and 1.6 to 2.3 mg per 100 ml, respectively. Eating disorder during pregnancy may have caused Bartter-like syndrome and weight loss, and led to the same syndrome and intrauterine growth retardation in the offspring. Therefore, a hidden maternal eating disorder may underlie neonatal pseudo-Bartter syndrome.
Metabolic alkalosis is a rare event in neonatal infants, but we encountered four cases of hypokalemic metabolic alkalosis at our hospital in 2005 and 2006. One case of pseudo-Bartter syndrome in a maternal–fetal pair due to an undiagnosed maternal eating disorder has been described,1 and maternal eating disorder has since been suspected to underlie neonatal pseudo-Bartter syndrome.
A total of 4 of 153 low birth weight infants (2.6%) admitted to the neonatal intensive care unit (NICU) at Wakayama Medical University Hospital from January 2005 to December 2006 showed hypokalemic metabolic alkalosis on admission. Two were full-term, light for gestational age (LGA, birth weight <10th percentile) infants, and the other two were preterm, dichorionic-diamniotic (DD) twins, one of whom was appropriate for gestational age (AGA: 10th percentile ⩽birth weight <90th percentile) and another was small for gestational age (SGA: birth weight and height <10th percentile) with the umbilical cord marginally inserted.2 One of the two full-term infants was outborn and admitted to the NICU on day 1, whereas the other three infants were inborn and admitted on day 0. All the infants had hypokalemic, hypochloremic and hyponatremic metabolic alkalosis on admission (Table 1).
Clinical course of pregnancy
The three mothers had neither a family history of Bartter syndrome nor a past history of anorexia nervosa. All were primipara and none had polyhydramnios, gestation-induced hypertension and proteinuria. All the mothers lost weight during pregnancy and were lighter at delivery than before pregnancy (Table 2): body mass index (BMI) decreased from 19.6 to 15.8, 22.8 to 22.3 and 20.3 to 17.2, respectively, during pregnancy. Two of the three were emaciated at delivery, even though they were in late gestation. Hypokalemia and hypochloremia worsened as pregnancy proceeded from mid to late gestation. Serum albumin was low in all three mothers and blood chemistry in renal function tests gave abnormally high values in two (Table 2). All the mothers had repeatedly rushed into the restroom after meals during the hospital stay, sometimes while holding a bottle of water, but neither nurses nor doctors had seen them vomiting. Several stress factors were present during pregnancy: a wedding, marital discord, and resignation in case 1; weight consciousness, and a shift to living in the parental home for delivery (an old Japanese custom) in case 2; and a third in vitro fertilization-embryo transfer (IVF-ET), twin pregnancy and threatened preterm birth in the mother of cases 3 and 4. Two mothers underwent emergency cesarean section because of intrauterine growth restriction (IUGR), oligohydramnios and non-reassuring fetal status. The abnormal blood chemistry had improved by 9 days after delivery.
Present illness and clinical course
Three of the four neonates had hypoalbuminemia, and the twins showed elevated levels in renal function tests. Low blood levels of sodium, potassium, chloride and albumin, metabolic alkalosis, and elevated levels in renal function tests had normalized by day 8. Three of the four neonates showed poor feeding and/or apnea, both of which disappeared by day 4. An ultrasound examination did not show hemorrhage, periventricular high-echogenicity in the brain or blood flow abnormalities in the kidneys in any patients. Routine blood tests including a hemogram, blood sugar, ionized calcium, ammonia and C-reactive protein were within the normal range. The twin with the most severe alkalosis (standard base excess, sBE: 20.7 mequiv. l−1) on day 0 showed cardiac failure due to patent ductus arteriosus (PDA) on day 1. Urine output was no less than 2 ml kg−1 h−1 and renal arterial blood flow was well maintained in color Doppler echography, which indicated that the elevated serum creatinine of 1.9 mg per 100 ml (which was attributed to a high maternal value) did not interfere with indomethacin administration. In fact, indomethacin infusion was ineffective on day 2. BE was rapidly reduced to −1.8 mequiv. l−1 due to cardiac failure and apnea did not appear. The PDA was ligated surgically on day 3 (Table 3).
Urine Cl/Cr ratios (mequiv. mg−1) and serum Mg (reference range: 1.4 to 2.0 mg per 100 ml) were <0.1 and 1.6 to 2.3 mg per 100 ml, respectively, in all four infants, leading to diagnosis of hypokalemic alkalosis as pseudo-Bartter syndrome in these four neonates. After 1-year follow-up, the four infants are healthy and the three mothers have had no recurrence of eating disorder or emaciation.
Hypokalemic alkalosis caused by genetic abnormalities in ion transporters of renal tubular cells is referred to as Bartter syndrome, or Gitelman syndrome when combined with hypomagnesemia. Bartter syndrome includes a classical type (type 3) and more severe neonatal types (types 1, 2 and 4). Long-term administration of diuretic agents or prostaglandin E (PG-E) and prolonged vomiting or diarrhea may result in a similar condition, which is called pseudo-Bartter syndrome; however, the three mothers in our cases received neither diuretics nor PG-E. Urinary Cl excretion is increased in Bartter syndrome but decreased in pseudo-Bartter syndrome, and this is useful for differentiation of these conditions when chronic vomiting gives symptoms similar to Bartter syndrome.3 The 2.5 and 50th percentiles for the urinary Cl/Cre ratio in normal infants are 0.073 and 0.185 mequiv. mg−1, respectively,4 and in our cases this ratio was below 0.1 in all four infants. Urine Cl was not measured in the mothers.
Maternal weight loss associated with hyperemesis gravidarum has been reported to be a predictor of IUGR.5 Hyperemesis gravidarum typically occurs in early gestation, but in our cases weight loss and laboratory data for the mothers worsened in late gestation compared to the midgestational period. Vomiting was not observed directly, but we assumed that vomiting occurred behind the closed door of the restroom based on the behavior of the mothers after meals. Other possible causes of hypochloremic alkalosis, weight loss and repetitive bathroom use include chronic laxative and diuretic use. In the absence of observation of the behavior and urine chloride measurement, an eating disorder appears to be the most likely cause, as Bartter syndrome has a much lower frequency and is not typically associated with weight loss and emaciation. Abnormal blood chemistry and weight loss resolved after delivery. Body fluid loss due to vomiting probably caused Bartter-like syndrome,1 hypoproteinemia, and prerenal renal failure in the mothers, and Bartter-like syndrome and sustained malnutrition for more than 10 weeks were probably related to the development of neonatal pseudo-Bartter syndrome and IUGR in the two full-term infants. The other two infants were preterm DD twins: one was AGA and the other was SGA complicated with marginal insertion of the cord.
The preterm twin with moderate alkalosis showed apnea and the twin with the most severe alkalosis developed cardiac failure due to PDA, became acidemic soon after birth, and did not show apnea. The term infant with greater alkalosis also showed apnea. Taken together, these results suggest that alkalosis may be related to apnea,6 as there were no clear abnormalities in clinical tests for assessment of the cause of apnea.
A national survey on nutrition in Japan (Ministry of Health, Labor, and Welfare. National Survey on Health and Nutrition, 2003. http://www.mhlw.go.jp/toukei/itiran/index.html) showed that emaciation defined by a BMI of less than 18.5 was most common in females in their twenties: 23.4% in 2003. In 2005, it was reported that birth weight had decreased by 0.18 kg over the past 25 years in Japan, and the percentage of low birth weight infants has increased from 5.2 to 9.5%.7 Japanese females are currently following a culture of thinness, and pregnant women may be no exception. Marital troubles, treatment for infertility, multiple pregnancy, threatened abortion or preterm labor or moving to the parental home for upcoming delivery can lead to stress during pregnancy. These problems may influence pregnant women and they may try to maintain the eating habits of other women. Vomiting can appear as a means of staying in shape, as an expression of their difficult situation, or as a way of obtaining a kind of catharsis. All the mothers in the current cases recovered from the eating disorder after delivery as their pregnancy-related difficulties ended.
As maternal eating disorder may progress latently during pregnancy and cause development of IUGR or fetal distress in offspring, monitoring of body weight and careful counseling are essential for pregnant women in a weight-conscious country.
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About this article
Neonatal Pseudo-Bartter's Syndrome with Hypokalemia and ECG Changes Born to a Mother with Eating Disorder: A Case Report
JOURNAL OF THE JAPANESE ASSOCIATION OF RURAL MEDICINE (2017)
Le syndrome de pseudo-Bartter néonatal dû à des désordres alimentaires maternels: peut-être plus fréquent qu’il n’y paraît
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