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Purpose: Late onset neonatal hypocalcemia (LNH) is defined as hypocalcemia detected after day 3 of life. Its occurrence in babies fed with cow’s milk is well understood. Since the advent of modern-day formulas, the incidence has however decreased. Methods: A prospective descriptive study (January 2017 to December 2017) of LNH seizures in neonates was conducted. LNH was defined as the total serum calcium of less than 7 mg/dL in preterm or less than 8 mg/dL in term newborns after 72 h of life. Results: 14 neonates were presented with myoclonic and focal seizures due to late hypocalcemia. All were formula fed. Their mean serum calcium, phosphorus, alkaline phosphatase, magnesium, 25-OH vitamin D, intact PTH levels were 4.93 mg/dL, 9.19 mg/dL, 244 U/L, 1.2 mg/dL, 30 nmol/L, 38.6 pg/mL, respectively. Mean maternal vitamin D levels were 43 nmol/L. Mean hospital stay was 4 days. Clinical response to treatment was brisk in those who were able to shift to total breast feeding early. Conclusions: LNH in formula-fed and vitamin D deficient babies is not uncommon. Emphasis should be laid on exclusive breast feeding even in vitamin D deplete mothers. However, mothers at risk should be supplemented with vitamin D during pregnancy.

Calcium, the most abundant ion in the neonate, plays a role in bone formation, blood coagulation, muscle contractility, and nerve conduction. Calcium levels are regulated via a negative feedback loop by the parathyroid hormone, calcitonin, and vitamin D. Calcium levels in the neonate must be monitored carefully to avoid complications that affect the central nervous system as well as the cardiac and musculoskeletal systems.

Infants with neonatal hypocalcemia often present with seizures, and neonatal hypocalcemia can be due to parathyroid (PTH) insufficiency or resistance. Causes of hypocalcemia with PTH elevation include increased phosphate load, vitamin D deficiency (VDD) or defects in metabolism, renal dysfunction, hypomagnesemia, genetic mutations resulting in end-organ resistance to PTH, or critical illness. Hypocalcemia has also been shown to be associated with Gram-negative bacteremia and sepsis in adults. We present the case of a full-term, formula-fed newborn presenting with late-onset hypocalcemic seizures and VDD in the setting of Klebsiella pneumoniae bacteremia. This case highlights that newborns presenting with hypocalcemic seizures should undergo a workup for sepsis.

Neonatal hypocalcaemia is defined as serum calcium (S-Ca) < 2.0 mmol/L in fullterm newborns and < 1.75 mmol/L in preterm newborns. Neonatal hypocalcaemia is either early onset (3 days of age). Newborns with hypocalcaemia are often asymptomatic, but may present with hypotonia, apnea, poor feeding, jitteriness, seizures, and cardiac failure. Signs of hypocalcaemia rarely occur unless S-Ca drops below 1.75 mmol/L. Neonatal hypocalcaemia can be a result of hypoparathyroidism (transient or primary), increased serum calcitonin, sepsis, asphyxia, hepatopathy, hypomagnesaemia, high phosphate load, transient hypoparathyroidism, and, rarely, transient neonatal pseudohypoparathyroidism (transient resistance to biological actions of parathyroid hormone [PTH]). We present three boys (two with gestational age 39 weeks, one 36 weeks; none of them with either asphyxia or sepsis) with mild hypotonia, where S-Ca in the range of 1.67-1.9 mmol/L was detected within the first three days of life, together with hyperphosphataemia (serum phosphate [P] 2.5-2.6 mmol/L), normomagnesaemia (serum magnesium [Mg] 0.77-0.88 mmol/L), normal alkaline phosphatase (ALP) activity (2.8-4.5 µkat/L) and high serum PTH (40-51 pg/mL; normal = 5-28). In spite of gradual increase of S-Ca, the elevated serum PTH persisted beyond days 3, 4 and 6 in all three boys, together with normal or low-to-normal S-Ca, high or normal-to-high serum P and no increases in serum ALP. The mothers´ S-Ca, P, Mg, ALP, PTH levels were within normal reference ranges. With regard to laboratory results, the diagnosis of transient neonatal pseudohypoparathyroidism (due to immaturity of PTH-receptors) is highly probable.in these three neonates.

Neonatal hypocalcemia and congenital heart defects has been known as the first clinical manifestation of the chromosome 22q11.2 deletion syndrome (22q11DS). However, because of its wide clinical spectrum, diagnosis of 22q11DS can be delayed in children without classic symptoms. We report the case of a girl with the history of imperforate anus but without neonatal hypocalcemia or major cardiac anomaly, who was diagnosed for 22q11DS at the age of 11 after the onset of overt hypocalcemia. She was born uneventfully from phenotypically normal Korean parents. Imperforate anus and partial cleft palate were found at birth, which were surgically repaired thereafter. There was no history of neonatal hypocalcemia, and karyotyping by GTG banding was normal. At the age of 11, hypocalcemia (serum calcium, 5.0 mg/dL) and decreased parathyroid hormone level (10.8 pg/mL) was noted when she visited our Emergency Department for fever and vomiting. The 22q11DS was suspected because of her mild mental retardation and velopharyngeal insufficiency, and a microdeletion on chromosome 22q11.2 was confirmed by fluorescence in situ hybridization. The 22q11DS should be considered in the differential diagnosis of hypocalcemia at any age because of its wide clinical spectrum.

Introduction: The most prevalent anomalous physical finding during the first week of life is neonatal hyperbilirubinemia (NNH). It is estimated that more than two thirds of newborn babies have acquired clinical jaundice. It was also discovered that in the unconjugated hyperbilirubinemia of most neonates represents a common or exaggerated physiological syndrome. The physical immaturity of infants to handle increased production of bilirubin is referred to as Jaundice. This becomes potentially neurotoxic if severe unconjugated hyperbilirubinemia is left untreated. One of the routine strategies for treating hyperbilirubinemia is known as phototherapy. However it is not a harmless interference. This can produce negative results, such as dehydration, temperature volatility, blood flow redistribution, genotoxicity, rashes on the skin, loose skin, stools, damage to retinas, hypocalcemia and bronze baby syndrome. One of the lesser known but which has a potential adverse effect of phototherapy is hypocalcemia. A total serum calcium concentration of < 7 mg / dl or ionised calcium concentration < 4mg / dl (< 1mol / L) is classified as neonatal hypocalcemia. Hypocalcemia increases the permeability of cells to sodium ions and increases the excitability of cell membranes. Material & Methods: 60 full term neonates were included in present cross sectional study who was admitted to Neonatal Intensive Care Unit (NICU). Full term neonates who completed 37 weeks of gestation with unconjugated hyperbilirubinemia who require phototherapy. Under the normal protocol, traditional phototherapy equipment containing four blue light fluorescent lamps with wavelengths of 410-470 nm was mounted at a distance of 25-35 cm from the skin surface of neonates with entirely covered eyes and genitals. At 15μW / cm2 /nm at the level of the infant's skin, the irradiance during phototherapy was assessed and maintained consistently. Results: Among 60 neonates included in this study there were 27 (45%) male whereas 33 (55%) female neonates. In present study the mean levels of serum calcium before phototherapy was 9.21 with standard deviation of 0.83 while the serum calcium levels after phototherapy were 8.36 with standard deviation of 0.78. There was a statistically significant difference between serum mean calcium levels before and after phototherapy (p=0.001). Conclusion: A major issue is phototherapy induced hypocalcemia. Before beginning and during phototherapy for neonatal jaundice and close monitoring of neonates for signs of hypocalcemia, careful calcium status calculation should be carried out.. After phototherapy, there is a substantial reduction in the amount of serum calcium, but the risk of hypocalcemia in stable full-term neonates is minimal.

Context Familial hypocalciuric hypercalcemia type 1 (FHH1) is caused by loss-of-function mutations of the calcium-sensing receptor (CaSR) and is considered a benign condition associated with mild-to-moderate hypercalcemia. However, the children of parents with FHH1 can develop a variety of disorders of calcium homeostasis in infancy. Objective The objective of this work is to characterize the range of calcitropic phenotypes in the children of a mother with FHH1. Methods A 3-generation FHH kindred was assessed by clinical, biochemical, and mutational analysis following informed consent. Results The FHH kindred comprised a hypercalcemic man and his daughter who had hypercalcemia and hypocalciuria, and her 4 children, 2 of whom had asymptomatic hypercalcemia, 1 was normocalcemic, and 1 suffered from transient neonatal hypocalcemia and seizures. The hypocalcemic infant had a serum calcium of 1.57 mmol/L (6.28 mg/dL); normal, 2.0 to 2.8 mmol/L (8.0-11.2 mg/dL) and parathyroid hormone of 2.2 pmol/L; normal 1.0 to 9.3 pmol/L, and required treatment with intravenous calcium gluconate infusions. A novel heterozygous p.Ser448Pro CaSR variant was identified in the hypercalcemic individuals, but not the children with hypocalcemia or normocalcemia. Three-dimensional modeling predicted the p.Ser448Pro variant to disrupt a hydrogen bond interaction within the CaSR extracellular domain. The variant Pro448 CaSR, when expressed in HEK293 cells, significantly impaired CaSR-mediated intracellular calcium mobilization and mitogen-activated protein kinase responses following stimulation with extracellular calcium, thereby demonstrating it to represent a loss-of-function mutation. Conclusions Thus, children of a mother with FHH1 can develop hypercalcemia or transient neonatal hypocalcemia, depending on the underlying inherited CaSR mutation, and require investigations for serum calcium and CaSR mutations in early childhood.

Background This study investigated the evolution of hypocalcemia with age and its associated risk factors in patients with 22q11.2 deletion syndrome (22qDS) and congenital heart defects. Method A retrospective review of the medical records of 16 22qDS patients (nine female, seven male; age range, 20.5-43 years) was performed. The frequency of hypocalcemia, as well as the clinical course of the disease and the presence of other phenotypes, were investigated. Results Ten of the 16 patients (62.5%) had a history of hypocalcemia. Among the 10 patients, the first onset of hypocalcemia occurred in the following developmental periods: neonatal stage, n = 1; early childhood, n = 3; late childhood, n = 2; adolescence, n = 2; and adulthood, n = 2. Neonatal hypocalcemia was observed in one patient, but it was transient. Two patients had sustained hypocalcemia after cardiac surgery. Hypocalcemia in one patient was transient following cardiac surgery, but it recurred during early adulthood. One patient developed hypocalcemia at 43 years of age. Thymus defect tended to be correlated with history of hypocalcemia (P = 0.09). This condition was often transient (60%) and was triggered by physical stress, such as intracardiac surgery. Conclusion In 22qDS patients, hypocalcemia was often mild and transient during childhood, but it may recur in adulthood. Routine clinical measurement of serum calcium is recommended, particularly in 22qDS patients with thymic defect or in patients who are under physical stress.

PubMed: 28610460 Objective: Vitamin D has many important functions in our body. Especially in intrauterine and early infancy periods, Vitamin D plays a major role in bone development, growth, and the maturation of tissues such as lung and brain. Fetus is dependent on the mother in terms of Vitamin D and maternal Vitamin D deficiency results in a Vitamin D deficient newborn. The purpose of this study was to determine the levels of Vitamin D in newborns and to investigate the association between Vitamin D status of the baby and neonatal hypocalcemia. Method: Vitamin D, calcium, and parathyroid hormone levels of 750 infants, born between 1 January 2014 and 30 June 2015 and followed in Ondokuz Mayıs University Neonatal Intensive Care Unit were analyzed retrospectively. Blood levels of Vitamin D were checked within 3 days after birth. A 25(OH)D3 level of 30 ng/ml) 25(OH)D3 levels; 68 (9%) had mild, 234 (31%) had moderate and 418 (56%) had severe vitamin D deficiency. No correlation was found between Vitamin D levels and gender, mother’s age, gestational week or birth weight. In 79 (17.2%) preterms, neonatal hypocalcemia was observed. Vitamin D levels of the premature infants who had early neonatal hypocalcemia were statistically significantly lower when compared with those who did not have early neonatal hypocalcemia (p =.02). No significant difference was found between the Vitamin D levels of the term infants who had early neonatal hypocalcemia and those who did not (p=.29). No significant difference was found between the Vitamin D levels of the infants who had late neonatal hypocalcemia and those who did not (in preterm p =.27; in term p =.29). Conclusions: Although lack of Vitamin D is preventable and curable, it is an important health problem for newborns in Turkey. In our study, 56% of the infants were found to have severe lack of Vitamin D and lack of Vitamin D was found to be associated with early neonatal hypocalcemia in preterm newborns. However, long-term effects of lack of Vitamin D in infancy are not fully known. In order to be able to prevent neonatal Vitamin D deficiency, 1200 IU/day vitamin D was supplemented to mothers from the 12th gestational week to 6th month of the birth, which was put into effect by the Ministry of Health in 2011, and should be applied by all health workers. © 2017 Informa UK Limited, trading as Taylor & Francis Group.

Infants born from mothers with Gestational diabetes mellitus (GDM) experience several complications, including a higher rate of postnatal hypocalcemia. In this study, we investigated the association between calcium sensing receptor (CaSR) and neonatal hypocalcemia observed in GDM pregnancies.Our study consisted of 58 pregnant women with GDM and 40 healthy women and their neonates. CaSR placental expression was evaluated with immunohistochemistry and Western Blot. Three CaSR single nucleotide polymorphisms, A986S, R990G, Q1011E, were evaluated in neonate's genomic DNA. Serum Ca, P, Mg, 25(OH)D and PTH were measured in cord blood and at 2nd day of life.GDM neonates had lower mean cord blood Ca levels than controls (2.47 ± 0.21 mmol/l vs 2.59 ± 0.13 mmol/l, p = 0.001) while 15.5% developed postnatal hypocalcemia. CaSR expression was lower in GDM than in healthy placentas (p0.001). In the GDM group, reduced CaSR immunostaining in the syncytiotrophoblast (p = 0.042) and extravillous cytotrophoblasts (p = 0.002) was associated with lower Ca cord blood levels. Moreover, the absence of the S allele of the A986S polymorphism was associated with lower serum Ca levels both at birth (AA:2.41 ± 0.23 mmol/l, AS + SS: 2.57 ± 0.12 mmol/l, p = 0.002) and at 2nd day of life (AA:2.05 ± 0.22 mmol/l, AS + SS: 2.20 ± 0.18 mmol/l, p = 0.019).Our results showed that CaSR is under-expressed in GDM compared with healthy placentas and this alteration may be associated with the lower Ca levels measured in cord blood of GDM infants. Placental CaSR seems to exert a local effect in fetal Ca homeostasis, which is dissociated from its contribution to the regulation of Ca homeostasis in postnatal life.

Hypocalcemia is a common endocrinological condition in 22q11.2 deletion syndrome. Neonatal hypocalcemia may affect neurodevelopment. We hypothesized that neonatal hypocalcemia would be associated with rare, more severe forms of intellectual disability in 22q11.2 deletion syndrome.We used a logistic regression model to investigate potential predictors of intellectual disability severity, including neonatal hypocalcemia, neonatal seizures, and complex congenital heart disease, e.g., interrupted aortic arch, in 149 adults with 22q11.2 deletion syndrome. Ten subjects had moderate-to-severe intellectual disability.The model was highly significant (P0.0001), showing neonatal seizures (P = 0.0018) and neonatal hypocalcemia (P = 0.047) to be significant predictors of a more severe level of intellectual disability. Neonatal seizures were significantly associated with neonatal hypocalcemia in the entire sample (P0.0001), regardless of intellectual level. There was no evidence for the association of moderate-to-severe intellectual disability with other factors such as major structural brain malformations in this sample.The results suggest that neonatal seizures may increase the risk for more severe intellectual deficits in 22q11.2 deletion syndrome, likely mediated by neonatal hypocalcemia. Neonatal hypocalcemia often remains unrecognized until the postseizure period, when damage to neurons may already have occurred. These findings support the importance of early recognition and treatment of neonatal hypocalcemia and potentially neonatal screening for 22q11.2 deletions.

Vitamin D has an important role in bone-metabolism (and its deficiency can cause preterm osteopenia, craniotabe and rickets), but it has also non-calcitropic functions. In fact, vitamin D deficiency is correlated to chronic kidney disease, respiratory infections, type 1 diabetes, psoriasis, Crohn disease and neonatal hypocalcemia. Because of the vitamin D deficiency is a global problem, its role as a drug is fundamental for the human health in all ages.

Calcium gluconate has been widely used in the management of neonatal hypocalcemia. When extravasation of a calcium gluconate infusion occurs, there may be rapid and marked swelling, erythema, and signs of soft tissue necrosis or infection, with ensuing extensive local calcifi cation, called calcinosis cutis. In most cases, calcinosis cutis following extravasation of calcium gluconate can be treated conservatively without any special treatment. However, it is often diffi cult to make a proper diagnosis because the disease is rare in the orthopedic fi eld, there is a time discrepancy between the clinical symptoms and radiographic fi ndings, and most patients are neonates. There are only two reports of this disease in the orthopedic literature. This report describes a neonate with “calcinosis cutis” following extravasation of calcium gluconate. The patient’s family was informed that the data from this case would be submitted for publication, and they gave their consent.

Pseudohypoparathyroidism (PHP) is a rare inherited syndrome characterized by parathyroid hormone (PTH) resistance and is frequently associated with Albright’s hereditary osteodystrophy and resistance to other cAMP-mediated hormones. The usual neonatal presentation is mild primary hypothyroidism secondary to resistance to thyroid-stimulating hormone; hypocalcemia usually develops after age 3–5 years. This work describes the diversity in the clinical expression and course of PHP, with emphasis on calcium levels by age and treatment, in 8 children under long-term follow-up at our pediatric tertiary center. The calcium levels at presentation ranged from transient neonatal hypocalcemia to infantile hypercalcemia to childhood/adolescence hypocalcemia. Interestingly, relative hypocalciuria at diagnosis and during therapy, in the presence of renal PTH resistance, was the rule. These findings indicate that transient neonatal hypocalcemia associated with other clinical features or a family history of PHP may be a flag for clinicians to screen for PTH resistance later in life. In addition, PTH resistance may be missed by surveying calcium levels only; thus the PTH levels have to be checked as well. In addition, the recommendation for patients with hypoparathyroidism that strict low-normal calcium levels be maintained during therapy in order to prevent hypercalciuria is probably not applicable in PHP.

Background Hypocalcemia is a frequent abnormality that has been associated with disease severity and outcome in hospitalized foals. However, the pathogenesis of equine neonatal hypocalcemia is poorly understood. Hypovitaminosis D in critically ill people has been linked to hypocalcemia and mortality; however, information on vitamin D metabolites and their association with clinical findings and outcome in critically ill foals is lacking. The goal of this study was to determine the prevalence of vitamin D deficiency (hypovitaminosis D) and its association with serum calcium, phosphorus, and parathyroid hormone (PTH) concentrations, disease severity, and mortality in hospitalized newborn foals. Methods and Results One hundred newborn foals ≤72 hours old divided into hospitalized (n = 83; 59 septic, 24 sick non-septic [SNS]) and healthy (n = 17) groups were included. Blood samples were collected on admission to measure serum 25-hydroxyvitamin D3 [25(OH)D3], 1,25-dihydroxyvitamin D3 [1,25(OH) 2D3], and PTH concentrations. Data were analyzed by nonparametric methods and univariate logistic regression. The prevalence of hypovitaminosis D [defined as 25(OH)D3

During pregnancy maternal serum concentrations of 25 hydroxyvitamin D correlate with dietary vitamin D intake. Maternal serum concentrations of 1.25-dihydroxyvitamin D the hormonal circulating and active form of vitamin D are elevated, during pregnancy. 1.25-dihydoxyvitamin D is synthesized mainly by the decidual cells of the placenta and allows for increased calcium absorption. The fetus is entirely dependent on the mother for its supply of 25 (OH) D which is believed to cross easily the placenta. Vitamin D deficiency during pregnancy affects the fetus and the newborn. Birth weight is decreased, bone mineralization is impaired and neonatal hypocalcemia is frequent. In countries where dairy products are not routinely supplemented in vitamin D maternal vitamin D supplementation during pregnancy is necessary.

Normal fetal and neonatal calcium homeostasis is dependent upon an adequate supply of calcium from maternal sources. Both maternal hypercalcemia and hypocalcemia can cause metabolic bone disease or disorders of calcium homeostasis in neonates. Maternal hypercalcemia can suppress fetal parathyroid function and cause neonatal hypocalcemia. Conversely, maternal hypocalcemia can stimulate fetal parathyroid tissue causing bone demineralization. We report two asymptomatic women, one with previously unrecognized hypoparathyroidism and the other with unrecognized familial benign hypercalcemia, who were diagnosed when their newborn infants presented with abnormalities of calcium metabolism. J.B. was born at 34 weeks' gestation with transient hyperbilirubinemia and thrombocytopenia. At 1 month of age he had severe bone demineralization, cortical irregularities, widening and cupping of the metaphyses, and lucent bands in the scapulae. The total serum calcium and phosphorus were normal with an ionized calcium of 5.4 mg/dL (4.6-5.4). His alkaline phosphatase, parathyroid hormone, and 1,25-dihydroxyvitamin D levels were all increased. P.B., mother of J.B., had no symptoms of hypocalcemia either prior to, or during this pregnancy. She had severe hypocalcemia and hyperphosphatemia, laboratory values typical of hypoparathyroidism. J.N. presented at 6 weeks of age with new onset of seizures and tetany secondary to severe hypocalcemia. The serum phosphorus, creatinine, alkaline phosphatase, and parathyroid hormone levels were normal. At 15 weeks of age his calcium was slightly elevated with a low fractional excretion of calcium. P.N., mother of J.N., had no symptoms of hypercalcemia either prior to, or during this pregnancy. Her serum calcium was 12.7 mg/dL and urine calcium was 66.5 mg/24 hr, with a low fractional excretion of calcium ranging from 0.0064 to 0.0073. P.N. has a brother who previously had parathyroid surgery. Both J.N. and P.N. meet the diagnostic criteria for familial benign hypercalcemia. These cases illustrate the important relationships between maternal serum calcium levels and neonatal calcium homeostasis. They emphasize the need to assess maternal calcium levels when infants are born with abnormal serum calcium levels or metabolic bone disease.

Neonatal seizures caused by hypocalcemia may be associated with cardiopulmonary dysfunction and may require specific management other than calcium supplementation. Severe dilated cardiomyopathy is an extremely rare complication in neonatal hypocalcemia and often results in high morbidity and mortality. We report here a 14-day-old neonate presenting with a gradually increasing frequency of tonic seizures. After admission, arterial desaturation was found despite supplying oxygen (4 L/min) through nasal prongs and the patient developed life-threatening respiratory distress and heart failure secondary to dilated cardiomyopathy. His critical cardiopulmonary derangements rapidly improved after respiratory support, the administration of diuretic and inotropic drugs, and the correction of his hypocalcemia and hypomagnesemia. The patient responded to treatment and was well during the 1-year follow-up period. We present this unique case history of seizure, respiratory distress, and heart failure induced by transient hypocalcemia to remind clinicians about the importance of this rare, life-threatening, but reversible, disorder.

ObjectiveTo characterize the endocrine and autoimmune disturbances with emphasis on parathyroid dysfunction in patients with 22q11.2 deletion syndrome (22q11.2 DS).DesignIn this nationwide survey; 59 patients (age 1–54 years) out of 86 invited with a 22q11.2 DS were recruited through all the genetic institutes in Norway.MethodsData was collected from blood tests, medical records, a physical examination and a semi-structured interview. We registered autoimmune diseases and measured autoantibodies, hormone levels and HLA types.ResultsTwenty-eight (47%) patients had hypoparathyroidism or a history of neonatal or transient hypocalcemia. Fifteen patients had neonatal hypocalcemia. Fourteen patients had permanent hypoparathyroidism including seven (54%) of those above age 15 years. A history of neonatal hypocalcemia did not predict later occurring hypoparathyroidism. Parathyroid hormone levels were generally low indicating a low reserve capacity. Twenty-eight patients were positive for autoantibodies. Six (10%) persons had developed an autoimmune disease, and all were females (PPConclusionsHypoparathyroidism and autoimmunity occur frequently in the 22q11.2 DS. Neonatal hypocalcemia is not associated with later development of permanent hypoparathyroidism. Hypoparathyroidism may present at any age, also in adults, and warrants regular measurement of calcium levels. Hypoparathyroidism and autoimmunity occur frequently together. Our findings of autoimmune diseases in 10% of the patients highlight the importance of stringent screening and follow-up routines.

Four children; all between 10-40 days of age, were admitted with multiple episodes of multifocal seizure. After admission blood investigation was carried out and they were found to have hypocalcemia, hyperphosphatemia; kidney function tests were normal. Serum parathyroid hormone was highly elevated and serum magnesium level was found to be normal in these patients. The infants did not have any other features of pseudohypoparathyroidism. The seizure was initially resistant to intravenous calcium therapy and later responded to oral calcitriol and calcium therapy. The diagnosis of pseudohypoparathyroidism was made according to biochemical investigations. The infants were symptom-free during follow-up and the biochemistry reports were also normalized. One of the infants was also suffering from neonatal hepatitis, due to CMV infection.

In a previous study, we showed a renal resistance to PTH in preterm infants during their 1 st week of life. We proposed it could explain early neonatal hypocalcemia. Such renal resistance is well known in type 1 pseudohypoparathyroid patients and is explained by a defect of stimulatory GTP-dependant protein (Gs). To determine if functional immaturity in the Gs protein could be involved in PTH resistance, we studied 27 newborn babies: 7 full-term and 20 preterm babies. Biological activity of the Gs unit was determined on days 1 3 and 10 after delivery by bioassay. No correlation was found between the Gs unit activity and either gestation or birth weight at these dates. Eight infants had hypocalcemia and their Gs unit activity did not differ from those with normocalcemia. Furthermore, we showed that the Gs unit is active from 29 weeks of gestation. We conclude that the Gs protein appears not to be involved in the pathophysiology of early renal resistance to PTH and therefore in early neonatal hypocalcemia.

Background/Purpose Transient pseudohypoparathyroidism is a rare cause of late-onset hypocalcemia in neonates and infants. The purpose of this study was to investigate the clinical presentation and natural course of transient pseudohypoparathyroidism in neonates and infants. Methods From 1995 to 2006, 21 patients under 3 months of age were admitted to our department because of late-onset neonatal hypocalcemia. Among these, five were noted to have transient hypocalcemia, hyper-phosphatemia and elevated serum parathyroid hormone levels. Their clinical data, biochemical findings and natural course were thoroughly analyzed. Results All five patients were boys with increased neuromuscular irritability as their initial clinical manifestation. Initial biochemical data showed calcium 1.5 ± 0.16 mmol/L, phosphorus 9.6 ± 1.5 mg/dL, intact parathyroid hormone 182 ± 93 pg/mL and tubular reabsorption of phosphorus 94.8 ± 3.7%. Two of the patients had magnesium deficiency. After reduction of phosphorus intake and supplementation with calcium and/or magnesium as indicated, the biochemical derangements resolved in 28 ± 3 days. Conclusion Neuromuscular irritability is usually the initial clinical presentation of transient pseudohypoparathyroidism. Aside from delayed renal maturation, pseudohypoparathyroidism is also caused by magnesium deficiency. Such a disturbance usually resolves before 3 months of age.

Purpose: To review clinical symptoms, laboratory findings, and treatment of transi­ ent neonatal hypocalcemia. Method: Medical records of full­term (gestational age ≥37 weeks) neonates diagnos­ ed with hypocalcemia, aged 8 mg/ dL. Relative hypoparathyroidism was defined as hypocalcemia and hyperphospha­ temia with parathyroid hormone level within the normal range (10–65 pg/mL). Results: Of 68 included neonates, 62 were diagnosed with hypoparathyroidism with hypocalcemia and hyperphosphatemia, and 26 had seizures. Mean serum calcium level of the seizure group was 5.99 mg/dL, which was significantly lower than that of the non­seizure group (6.46 mg/dL, P=0.012). The recovery duration for calcium and phosphate levels was long, at 5.8 and 10.7 days, respectively. The calcium level reco­ very duration was significantly different between the seizure and non­ seizure groups (P=0.034), but the phosphate level recovery period was not significantly different (P=0.194). Of 17 patients with diarrhea, 10 had confirmed rotavirus infec tion. Most patients with hypocalcemia responded well to oral calcium lactate and intravenous calcium gluconate, and the treatments could be discontinued after a certain period. Conclusion: Transient neonatal hypocalcemia is associated with hypoparathyroi­ dism. The major symptom in late neonatal hypocalcemia was the occurrence of sei­ zures. Serum calcium level was lower and the recovery period was longer in the seizure group, but most cases exhibited favorable progress.

Prematurity, neonatal asphyxia, hypomagnesemia, and advanced maternal diabetes are traditional risk factors for hypocalcemia in infants of diabetic mothers (IDMs). The aim of this study was to determine the relative contribution of these factors separately and combined in a cohort of diabetic pregnancies managed prospectively in the recent 9 years and to find accurate predictors of neonatal hypocalcemia in infants of diabetic mothers. We hypothesized that these factors plus low cord blood calcium (Ca) concentration allow prediction of IDMs who develop neonatal hypocalcemia. We studied 186 IDMs (White class B-RT); gestational age (GA, weeks) was by last menstrual period, confirmed +/- 2 weeks by Ballard score. The goals of glycemic control were: preprandial blood glucose less than 100 mg/dl and 90-minute postprandial blood glucose less than 140 mg/dl. Apgar scores, and cord, 24-, 48- and 72-hour serum calcium (Ca) (mg/dl) and magnesium (Mg; mg/dl) were determined. In univariate analysis, lowest serum Ca correlated with cord blood Ca (r = 0.48, p less than 0.001), GA (r = 0.37, p less than 0.001), and 1-minute Apgar score (r = 0.18, p = 0.09), but did not correlate with cord Mg or with advanced White class. In multiple regression, cord Ca and GA were dominant effects and other variables became insignificant. Lowest Ca (mg/dl) was predicted as follows: lowest Ca = 34.05 - 3.22 (Ca cord) - 0.84 (GA) + 0.10 (GA) (Ca cord). This equation predicts neonatal hypocalcemia (lowest Ca less than 8 mg/dl) with a sensitivity of 72% and a specificity of 75%. Thus, GA and cord Ca allow determination of IDMs at risk for neonatal hypocalcemia.

Hypoparathyroidism is one of the recognized causes of late-onset neonatal hypocalcemia. Maternal hypercalcemic hyperparathyroidism has been shown to suppress fetal parathyroid glands, causing transient neonatal hypoparathyroidism. We report two siblings (6 years apart) with transient hypoparathyroidism presented with hypocalcemic seizures during the first 2 weeks of life. Subsequent investigation revealed an unrecognized normocalcemic hyperparathyroidism with nephrocalcinosis in the mother. Maternal hyperparathyroidism was caused by two parathyroid adenomas. In conclusion, our report highlights the importance of careful evaluation of neonatal hypoparathyroidism in uncovering an unrecognized, asymptomatic hyperparathyroidism in the mother.

Objective: Clinical features associated with microdeletion of chromosome 22q11 (del(22)(q11)) are highly variable. Increased awareness of this condition is needed among specialists such as endocrinologists to reduce diagnostic delay and improve clinical care. The purpose of this study was to describe the phenotype of patients with del(22)(q11), focusing on parathyroid gland dysfunction. Design and methods: Charts of 19 patients, including one kindred of three, known to have del(22)(q11) diagnosed by fluorescence in situ hybridization (FISH) were reviewed from the register of the department of Medical Genetics. Major clinical features including hypoparathyroidism phenotype were collected. Results: Parathyroid dysfunction was present in 8 out of 16 patients (50%). Six patients were diagnosed with overt hypoparathyroidism. Hypocalcemia manifested as laryngeal stridor within the first days of life (n=3), seizures in infancy (n=1) and adolescence (n=2). The connection between hypoparathyroidism and diagnosis of del(22)(q11) was belated at the median age of 18 years. One patient had presented with transient neonatal hypoparathyroidism, and one patient had latent hypoparathyroidism. Within the kindred family, the phenotype variability including that of parathyroid dysfunction was as marked as between unrelated individuals. Standard karyotype failed to detect the deletion in 15 out of 19 cases. Conclusions: Abnormal parathyroid function in the del(22)(q11) ranges from severe neonatal hypocalcemia to latent hypoparathyroidism. Del(22)(q11) should be considered as a potential cause of hypocalcemia even in young adult. When suspected, the diagnosis requires investigation by FISH. Furthermore, long-term calcemia follow-up is needed in normocalcemic patients with del(22)(q11) because of the possible evolution to hypocalcemic hypoparathyroidism.

The DiGeorge anomaly (DGA) is an etiologically heterogeneous developmental field defect in which cardiovascular malformations, hypocalcemia, thymic hypoplasia, and characteristic dysmorphisms are major clinical features. The 22q11.2 deletion is the most common single etiology of DGA, although a number of other chromosomal abnormalities and teratogens, including maternal diabetes, have been implicated as well. We present a patient, born to a diabetic mother, with interrupted aortic arch type B (IAA-B), neonatal hypocalcemia, thymic hypoplasia, and dysmorphic features including microcephaly, thick, overfolded helices, and anteriorly-placed anus. Cytogenetic studies showed the presence of a marker chromosome, identified by fluorescence in-situ hybridization (FISH) as an isochromosome 18p [i(18p)]. We did not detect a 22q11.2 deletion by FISH using a cosmid probe corresponding to locus D22S75. The patient is the first example of either DGA or IAA-B in a patient with i(18p). We review the genetic abnormalities associated with DGA, and discuss the potential contributions of maternal diabetes and i(18p) in our patient. © 2005 Wiley-Liss, Inc.

The occurrence of hypocalcemia in a term infant after the first few days of life is known to result from excessive dietary phosphate, hypomagnesemia, neonatal hypoparathyroidism, hypovitaminosis D, and maternal hyperparathyroidism. Less well recognized is the possibility that maternal ingestion of antacids may cause late neonatal hypocalcemia. Our observations suggest that taking large doses of calcium carbonate during pregnancy may be a potential cause of neonatal hypocalcemia. ( J Child Neurol 2002;17:853—855).

Familial hypocalciuric hypercalcemia (FHH) is a benign autosomal dominant disorder. Infants affected with FHH however, born to unaffected mothers may develop life-threatening autonomous hyperparathyroidism, the mechanism of which is not clearly understood. There is little information recorded in the literature regarding the opposite scenario, i.e., unaffected infants born to affected mothers. Because fetal parathyroid suppression presumably occurs secondary to high maternal calciums, neonatal hypocalcemia would be expected. The authors present a case of an infant with the latter circumstances who presents with late onset, life-threatening hypocalcemia secondary to relative hypoparathyroidism. The authors explored the possibility that vitamin D deficiency and/or acute environmental stress facilitated the decompensation. The patient required therapy for 2 months.

We conducted a prospective, double-blind study of 43 preterm infants to examine the effect of a single calcium gluconate infusion as therapy for neonatal hypocalcemia on serum calcium concentrations and hypocalcemic signs in preterm infants with low total serum calcium concentrations. Total and ionized serum calcium was measured and signs of irritability, jitteriness, and twitching were scored (scale 0-9) by blinded observers before and after receiving one dose of either calcium gluconate (100 mg/kg) or placebo (normal saline). Total and ionized serum calcium increased 3 to 6 hours following the calcium, but not the placebo, infusion. Of the infants with hypocalcemic signs, the average score of hypocalcemic signs decreased in the 11 calcium-treated infants; the 12 infants with hypocalcemic signs showed no change of hypocalcemic signs following treatment with placebo. We conclude from this study that a single dose of calcium gluconate (100 mg/kg) in hypocalcemic preterm infants raise total and ionized serum calcium and decrease clinical signs of hypocalcemia.

OBJECTIVE To test the hypothesis that strict control of diabetes during pregnancy can reduce the risk for neonatal hypocalcemia in infants of diabetic mothers. METHODS One hundred thirty-seven pregnant women with insulin-dependent diabetes enrolled before 9 weeks' gestation were randomized to one of two treatment groups. In 68 subjects, the goals were fasting blood glucose level less than 4.44 mmol/L (80 mg/dL) and 1.5-hour postprandial blood glucose level less than 6.66 mmol/L (120 mg/dL) (strict control), whereas in 69 the goals were fasting blood glucose level less than 5.55 mmol/L (100 mg/dL) and 1.5-hour post-prandial glucose level less than 7.77 mmol/L (140 mg/dL) (customary control). RESULTS Infants in the strict control group had a significantly lower rate of hypocalcemia (mean calcium less than 8.0 mg/dL in term infants and less than 7.0 mg/dL in preterm infants) than infants in the customary control group (17.6 versus 31.9%; P < .05). Using logistic regression analysis and after adjusting for the effects of gestational age, asphyxia, and White class on hypocalcemia, the difference between groups remained significant. The lowest infant serum calcium concentration correlated significantly with maternal glycohemoglobin A1 concentration at delivery (P = .03), gestational age (P = .0001), and the lowest serum magnesium concentration (P = .0001). CONCLUSION Strict management of diabetes in pregnancy is associated with a reduction in the rate of neonatal hypocalcemia.

In pregnant women with symptomatic hyperparathyroidism, parathyroidectomy should be undertaken during the second trimester. We feel that the woman who is initially diagnosed well into the third trimester should be treated medically unless the hypercalcemia worsens or other complications occur. Since the treatment of asymptomatic hyperparathyroidism itself is controversial, it is even more difficult to define the treatment plan for an asymptomatic pregnant patient who has primary hyperparathyroidism. However, a recent consensus panel recommended that young patients with asymptomatic hyperparathyroidism be treated surgically. Accordingly, we believe that the asymptomatic pregnant patient should also be treated surgically, preferably in the second trimester. Whether a patient is treated medically or surgically in these situations, the pregnancy should be considered high-risk. The neonate should be monitored carefully for signs of hypocalcemia or impending tetany. If the mother is treated medically to term (or if spontaneous or elective abortion occurs), the mother should be monitored for hyperparathyroid crisis postpartum. Sudden worsening of hypercalcemia can result from the loss of the placenta (active placental calcium transport may be somewhat protective) and dehydration. Finally, every effort should be made to make the definitive diagnosis early in pregnancy in order to initiate optimal management. The diagnosis should be suspected during pregnancy if the following conditions exist: appropriate clinical signs or symptoms (especially nephrolithiasis or pancreatitis), hyperemesis beyond the first trimester, history of recurrent spontaneous abortions/stillbirths or neonatal deaths, neonatal hypocalcemia or tetany, or a total serum calcium concentration greater than 10.1 mg/dL (2.52 mmol/L) or 8.8 mg/dL (2.2 mmol/L) during the second or third trimester, respectively.

Little is known of the factors regulating parathyroid function in the neonatal period. Twenty-seven term infants born after uncomplicated pregnancies, labors, and deliveries were studied to test the hypothesis that in normal newborns the amplitude of parathyroid hormone (PTH) response to decreasing serum ionized calcium (iCa) correlates with serum magnesium (Mg) concentrations. Serum iCa (ion selective electrode, Radiometer ICA 1), PTH (1-84 intact molecules, radioimmunoassay) and Mg (atomic absorption) were measured at birth (cord blood) and 24 hours of age. Repeated measures analysis of covariance showed decreasing serum iCa (p less than 0.01) and increasing serum Mg (p less than 0.01) and PTH (p less than 0.01) over time. The change in PTH over the first 24 hours was directly correlated with cord blood (r = 0.38, p less than 0.05) and 24-hr Mg concentrations (r = 0.53, p less than 0.01). We conclude that the ability of the parathyroid gland to respond to decreasing serum iCa after birth is directly related to Mg status. We speculate that neonatal hypomagnesemia may lead to a blunted PTH secretory response, thus contributing to early neonatal hypocalcemia.

The levels of 25(OH)D have been quantified in 42 insulin diabetic pregnancies (DP) through the three trimesters of pregnancy with a total of 177 determinations. In parallel we quantified this metabolite in 114 normal pregnant women (NP) and also in 116 normal controls (NC). In addition 25(OH)D was quantified in 18 (DP) and 19 (NP) at delivery in the 35-37th week of pregnancy, and ionic calcium was measured in their newborns at 24 h of life. Grouping by trimesters of gestation, the (NP) group had 25(OH)D levels similar to those of (NC) and none showed significant differences between trimesters of pregnancy. (DP) showed in all seasons lower (25(OH)D levels than (NC) but did not have differences in these levels between trimesters of pregnancy. The newborns of (DP) had lower ionic calcium levels than newborns of (NP). Eight newborns of (DP) had hypocalcemia and seven of their mothers showed 25(OH)D levels lower than 10 ng/ml. These findings suggest that lower 25(OH)D levels in (DP) can influence the neonatal hypocalcemia in their newborns.

It has been suggested that hypercalcitoninemia may contribute to neonatal hypocalcemia in infants of diabetic mothers (IDM). Because the role of calcitonin (CT) in Ca metabolism in humans is questionable, we hypothesized that serum CT peaks similarly after birth in IDM and controls and that serum Ca concentrations do not correlate with serum CT. Forty-seven term IDM (White classes B-RT) were compared with 31 controls. Controls were born after normal pregnancies, labors, and deliveries. Blood samples (cord and 24 h) were analyzed for Ca, Mg, parathyroid hormone (PTH), and CT. Repeated measures analysis showed increasing serum Mg, PTH, and CT, and decreasing Ca over time. The incidence of hypocalcemia was significantly higher in the diabetic group (p less than 0.01) and the incidence of hypomagnesemia was borderline significantly higher (p less than 0.06). There were no differences in cord or 24-h serum concentrations of CT between groups. In multiple regression analysis, serum Ca and PTH were correlated (p less than 0.02, R2 = 0.33), but not serum Ca and CT; the increase in serum PTH in relation to serum Ca at the nadir (24 h) correlated directly with serum Mg concentrations (R2 = 0.31, p less than 0.05). Thus, serum CT increases after birth irrespective of the rate of decrease of serum Ca in both IDM and controls; high CT concentrations observed after birth (as compared with adult norms) do not seem to play a role in the pathogenesis of neonatal hypocalcemia in IDM; and responsiveness of parathyroid gland at birth is adversely affected by hypomagnesemia, which supports the theory of functional hypoparathyroidism in Mg deficiency.

Diabetes mellitus is associated with a large number of abnormalities in calcium homeostasis: urinary calcium excretion in both human and experimental diabetes is increased; the duodenal calcium absorption is usually decreased in streptozotocin-induced diabetic rats and the duodenal calbindin concentration is similarly decreased (Table 1). The osteoblast function also seems to be impaired as suggested by decreased bone formation and possibly decreased bone mass in both experimental and human insulindependent diabetes mellitus (1). Moreover, the fetus or neonate of diabetic mothers have an increased risk for bone and calcium abnormalities, such as the caudal regression syndrome and neonatal hypocalcemia. The pathogenesis of these abnormalities is not well known. We, therefore, used the spontaneously diabetic BB rat, a model of human autoimmune diabetes, to study the effect of insulin deficiency on vitamin D and calcium homeostasis.

Background The neonate is susceptible to hypocalcemia from a variety of etiologies. At particular risk is the low birth weight or premature infant, those born to diabetic mothers and those who have increased perinatal stress. Case Report We report a two week old full term male infant with a 7 day history of twitching, jerking movements of the extremities. The mother reported respiratory and feeding difficulties one day prior to admission. The history was negative for fever, lethargy, emesis or diarrhea. Laboratory analysis revealed a serum calcium 6.3 mg/dL, ionized calcium 0.9 mmol/L, phosphorus 11.3 mg/dL, magnesium 1.2 mg/dL, and albumin 3.2 g/dL. The rest of her metabolic panel, liver function studies, CBC, CRP, chest x-ray, and CT scan of the brain were all within normal limits. The infant was admitted to the PICU and treated with a calcium gluconate infusion. Serum calcium increased to 10.6 mg/dL and phosphorus to 7 mg/dL. Symptoms resolved within 2 days. He was sent home on oral calcium supplements. Further investigation for the hypocalcemia of the infant revealed normal levels of PTH, vitamin D, and thyroid function studies. A workup on the mother was performed and demonstrated increased serum calcium 12.3 mg/dL, phosphorus 1.9 mg/dL, PTH 323 pg/dL (normal 15-75) and vitamin D 10 mg/mL. An ultrasound of the neck and radiothallium scanning revealed a parathyroid adenoma of the right superior gland. Discussion Neonatal hypocalcemia and tetany may be observed as a result of maternal hypercalcemia or hyperparathyroidism. There will generally be a prolonged but temporary suppression of parathyroid function in the infant. Hypocalcemia in a full term baby with no complications in pregnancy or perinatal history should prompt an investigation in the mother.

• We previously suggested that "late" neonatal hypocalcemia is related to a low calcium-phosphorus ratio of current cow's milk—based formula compared with human milk. However, there are no longitudinal studies of ionized calcium and parathyroid hormone concentrations in neonates receiving formulas with varying Ca/P ratios. Sixty-nine term neonates were studied through 2 weeks of age, and formula-fed neonates were randomized at birth to receive formula with molar ratios of 0.9,1.2, or 1.4. Serum phosphate concentrations on days 2 and 6 of age were higher, and ionized calcium levels lower on days 6 and 14, in formula-fed vs human milk—fed neonates. Serum intact parathyroid hormone level increased between days 2 and 6 in formula-fed neonates compared with a decrease in human milk—fed neonates. Serum parathyroid hormone level on day 6 correlated with phosphorus intake among formula-fed neonates. No differences were noted in serum mineral or hormone levels among formula-fed groups. We speculate that the lowering of serum ionized calcium concentrations in neonates fed a modern "humanized" cow's milk formula may be a factor in late neonatal hypocalcemia. ( AJDC . 1991;145:941-945)

The critical organs involved in perinatal calcium homeostasis (the placenta, intestine, kidney, and bone) are discussed. A physiologic approach is presented in order to provide an understanding of the disturbances of calcium metabolism.

Sixteen neonates, ranging in gestational age from 27 to 41 weeks and in postnatal age from birth to 8 days, were evaluated for their renal response to an endogenous PTH stimulus in 22 separate experiments. The PTH stimulus was generated by the decreased serum ionized Ca that accompanies exchange transfusion with citrated blood. The neonates increased their serum PTH from 95.8 +/- 13.1 to 133.9 +/- 15.4 microliterEq/ml (mean +/- SEM) during the transfusion, while increasing their urinary cAMP from 0.77 +/- 0.11 to 1.45 +/- 0.22 nmol/ml, and their urinary P from 12.9 +/- 2.6 to 30.6 +/- 6.1 mg/dl in the four hours following the exchange transfusion. This response was not related to postnatal or gestational age. We speculate that lack of renal responsiveness to PTH does not play a major role in the pathogenesis of early neonatal hypocalcemia.

To ascertain the activity of the vitamin D biosynthetic pathway, the serum concentration of 1,25-dihydroxyvitamin D (calcitriol) was measured in 16 preterm infants (32 to 37 weeks of gestation) at 1 to 2 and 120 hours of age. Half of the subjects received a daily oral supplement of 2,100 IU of vitamin D3 during the five-day study period. In the first two hours of life, all subjects were hypocalcemic (8.2 +/- 0.2 mg/dl) and 14 subjects had low concentrations of 25-hydroxyvitamin D (calcidiol, 8 +/- 1 ng/ml). The latter finding probably reflects a mild degree of vitamin D deficiency in the mothers of our subjects. Calcitriol concentrations (42 +/- 3 pg/ml) were comparable to those of older children. At 120 hours of age, the control group had no significant change in calcitriol values, whereas the group supplemented with D3 had a more than threefold increase. There was a positive correlation between the circulating concentrations of calcidiol and calcitriol over the period of the study. The data show that, after 32 weeks of gestation, renal 25-hydroxyvitamin D-1 alpha-hydroxylase activity is present, with the rate of calcitriol synthesis being apparently substrate limited. Early neonatal hypocalcemia is therefore unlikely to be caused by an impairment of vitamin D activation.

Electrolyte abnormalities in the neonate, such as hypocalcemia, hyperphosphatemia, hypomagnesemia, and alkalosis, can predispose to neuromuscular irritability. The pathophysiology of these disorders and techniques for measuring serum calcium, magnesium, and phosphorus are discussed.

Early neonatal hypocalcemia occurs in premature infants, infants with birth asphyxia, and infants of diabetic mothers. Etiological considerations include decreased calcium (Ca) supply, increased endogenous phosphate load, hypomagnesemia, alkali therapy, functional hypoparathyroidism, defects in vitamin D metabolism, and possibly calcitonin excess. Late neonatal hypocalcemia occurs, with malabsorption of magnesium (Mg), increased exogenous phosphate loading, after alkali therapy of diarrheal acidosis, hypoparathyroidism, and vitamin D related disorders. The therapy of hypocalcemia includes oral or iv Ca salts and in the near future, possibly the newly discovered vitamin D metabolites.

Serial serum Ca values in 47 infants with intrauterine growth retardation were analyzed in relation to clinical and biochemical factors. Serum Ca concentrations in IUGR infants fell within the 95 percent confidence limits for serum Ca in infants whose birth weights were appropriate for gestational age. Serum Ca concentrations in IUGR infants were significantly correlated with birth asphyxia and bicarbonate therapy for acidosis. Serum Ca concentration at 24 hours of age was inversely correlated with serum P values. Thus the incidence of neonatal hyocalcemia in IUGR infants is not increased above the incidence expected from their respective gestational ages. Infants with IUGR who are well at birth do not appear to develop neonatal hypocalcemia, but IUGR infants who are asphyxiated at birth develop significant hypocalcemia.

Treatment of hypocalcemia in the normotensive but moderately ill neonate has been associated with an increase in blood pressure and heart rate. Blood pressure increased within five minutes after the end of a parenteral bolus infusion of calcium and remained elevated for approximately 50 minutes before returning to pretreatment values. Heart rate increased by 20 minutes after calcium infusion and the effect lasted through 90 minutes. Arterial and venous infusions of calcium were both followed by similar elevations in blood pressure and heart rate whereas infusions of saline were followed by no changes in either heart rate or blood pressure. The absence of other obvious explanations for the acute blood pressure elevation suggests that the increases in blood pressure and heart rate are directly related to or indirectly mediated by calcium therapy.

Seventy-three premature and full-term infants were studied to determine the importance of gestational age, hyperphosphatemia, hypomagnesemia, increased urinary calcium losses, and parathormone responsiveness in the pathogenesis of neonatal hypocalcemia. Serum calcium values from 12 to 72 hours of age were significantly correlated with gestational age. Birth asphyxia and hyperphosphatemia at birth were associated with subsequent hypocalcemia. Serum calcium levels were unrelated to hypomagnesemia and urinary calcium losses. Significant calcemic responses to parathormone were elicited in 24 premature infants. This calcemic response was not related to gestational age or birth asphyxia but was more marked when serum calcium concentrations were lower. The study suggests that neonatal hypocalcemia results from functionally immature or suppressed parathyroids that are unable to maintain normocalcemia in the presence of hyperphosphatemia.

The functional capabilities of the neonatal parathyroid glands in relation to gestational age and postnatal age were studied in two groups of infants. In Group 1, the “serial group,” 19 infants of 30 to 37 weeks' gestational age and their respective mothers were studied from birth to determine changes in serum parathyroid hormone levels in relation to postnatal decreases in serum calcium concentrations. In Group 2, 16 infants, 30 to 42 weeks' gestational age, received exchange transfusions for hyperbilirubinemia; the changes in serum parathyroid hormone concentration during citrate-induced hypocalcemia were then determined. Parathyroid function was found to be impaired in infants of shortened gestational age and in infants during the first two days of life. Relatively high serum values of ionized calcium were found in cord blood of premature infants. It is speculated that fetal hypercalcemia is a factor in suppression of fetal parathyroid function. Restoration of usual serum calcium values is achieved when the neonatal parathyroid glands recover their normal function or mature postnatally.