CLINICAL PROFILE AND MATERNAL-NEONATAL RISK FACTORS ASSOCIATED WITH IONIZED HYPOCALCEMIA AMONG NEONATES ADMITTED TO A TERTIARY CARE NEONATAL INTENSIVE CARE UNIT: A PROSPECTIVE OBSERVATIONAL STUDY

One of the many metabolic problems that newborns experience is neonatal hypocalcaemia, which continues to be a significant cause of morbidity in neonates referred to neonatal intensive care units (NICUs). Neuromuscular transmission, myocardial contractility, blood coagulation, intracellular signalling, enzyme activation, and hormone production all depend on calcium. A wide range of clinical symptoms, including jitteriness, poor eating, apnoea, seizures, and cardiovascular instability, can result from a disruption in calcium homeostasis during the neonatal period. Foetal calcium concentrations are higher than maternal calcium concentrations because calcium is actively transferred across the placenta during foetal life. The third trimester is when the majority of foetal calcium accretion takes place. Because premature birth disrupts placental mineral transport, preterm neonates are more susceptible to hypocalcaemia,linked to immature parathyroid hormone response, decreased skeletal mineral storage, and immature kidneys.

 Early-onset hypocalcaemia, which happens within the first 72 hours of life, and late-onset hypocalcaemia, which happens after 72 hours, are the two main categories for neonatal hypocalcaemia. Prematurity, low birth weight, newborns of diabetic mothers, birth asphyxia, and neonatal infection are all frequently linked to early-onset hypocalcaemia. High phosphate consumption, vitamin D deficiency, hypomagnesaemia, and aberrant parathyroid hormone secretion or action are more frequently linked to late-onset hypocalcaemia. Ionised calcium is the physiologically active portion of calcium, even though total blood calcium has historically been utilised for diagnosis. Serum albumin levels, pH, and other biochemical changes can impact total calcium readings in severely sick newborns. Thus, ionised calcium measurement is especially helpful in NICU settings and provides a more accurate assessment of clinically severe hypocalcaemia.

Neonatal hypocalcaemia is caused by a number of maternal and neonatal causes. Infants may be at risk for temporary functional hypoparathyroidism if their mothers have diabetes mellitus. The severity of newborn disease or foetal mineral reserves may be indirectly impacted by pregnancy-induced hypertension, maternal anaemia, and protracted rupture of membranes. Impaired calcium homeostasis has been linked to neonatal conditions such prematurity, low birth weight, birth asphyxia, sepsis, delayed feeding, and respiratory disease. There is still a dearth of Indian data explicitly addressing ionised hypocalcaemia in newborns referred to the NICU, despite its clinical significance. Determining the clinical characteristics and risk factors of ionised hypocalcaemia may aid medical professionals in creating focused screening plans and starting prompt therapy. The goal of the current investigation was to assess the clinical characteristics,

AIM

To investigate the clinical characteristics and maternal-neonatal risk factors linked to ionised hypocalcaemia in newborns admitted to a neonatal critical care unit for tertiary treatment.

OBJECTIVES

·         To assess the clinical characteristics of newborns suffering from ionised hypocalcaemia.

·         To determine the risk variables for newborn ionised hypocalcaemia in mothers.

·         To determine the risk variables for newborn ionised hypocalcaemia.

·         To contrast neonates with ionised hypocalcaemia who are symptomatic and those who are not.

·         To evaluate the immediate results of ionised hypocalcaemia in newborns.

Study design and setting

Sree Mookambika Institute of Medical Sciences' Neonatal Intensive Care Unit in Kulasekaram, Tamil Nadu, India, was the site of this prospective observational study.

Study duration and sample size

The research was carried out over a ten-month period. 56 neonates who met the eligibility requirements and had proven ionised hypocalcaemia were included.

Inclusion criteria

Included were newborns with ionised hypocalcaemia who were admitted to the NICU. Ionised calcium levels less than 1.1 mmol/L in term neonates and less than 1.0 mmol/L in preterm neonates were considered ionised hypocalcaemia.

Exclusion criteria

Neonates with insufficient clinical records, those with significant congenital defects, and those who had undergone calcium treatment prior to admission were not included.

Data collection

A structured proforma was used to gather data. Anaemia, gestational diabetes mellitus, hypertension brought on by pregnancy, exposure to prenatal steroids, and protracted rupture of membranes lasting more than eighteen hours were among the maternal factors. Sex, gestational age, birth weight, prematurity, low birth weight status, birth asphyxia, neonatal sepsis, delayed feeding, infant-of-diabetic-mother status, mode of delivery, age at detection, and onset type were among the neonatal factors.

Clinical and biochemical assessment

Jitteriness, poor eating, convulsions, irritability, and apnoea were among the clinical characteristics evaluated. Ionised calcium, total serum calcium, serum magnesium, blood glucose, and a sepsis screen were among the laboratory measures. Hypocalcaemia was classified as either early-onset (detected within 72 hours of life) or late-onset (detected after 72 hours).

Outcome assessment

Improvement and discharge, longer than seven days in the NICU, referral or discharge upon request, and mortality were among the short-term outcomes.

Statistical analysis

SPSS version 26.0 was used to analyse the data, and Python-based statistical analysis was used to confirm the results. Categorical variables were expressed as frequencies and percentages, whereas continuous variables were expressed as mean ± standard deviation. Continuous variables were compared using the independent t-test. For categorical variables based on anticipated cell counts, the chi-square test or Fisher exact test were employed. For clinically significant predictors, odds ratios with 95% confidence intervals were computed. To find independent predictors of symptomatic hypocalcaemia, multivariable logistic regression was used. Statistical significance was defined as a p-value of less than 0.05.

Ethical considerations

After receiving approval from the Sree Mookambika Institute of Medical Sciences' Institutional Ethics Committee, the study was carried out. Throughout the trial, patient data confidentiality was upheld.

The investigation comprised 56 infants with verified ionised hypocalcaemia.

Table 1. Baseline demographic and neonatal characteristics

Table 2. Maternal risk factors

Table 3. Neonatal risk factors

Table 4. Clinical profile

Table 5. Biochemical and clinical course profile

Table 6. Comparison of continuous variables between symptomatic and asymptomatic neonates

Table 7. Comparison of categorical variables between symptomatic and asymptomatic neonates

Table 8. Univariate predictors of symptomatic ionized hypocalcemia

Table 9. Multivariable logistic regression for symptomatic hypocalcemia

Prematurity, neonatal sepsis, birth asphyxia, and male sex are among the variables that are part of the model. The updated model should be regarded as exploratory due to the small sample size.

Table 10. Short-term outcomes

There were 33 (58.9) male neonates in the research population, indicating a male predominance. The average birth weight was 2.38 ± 0.64 kg, and the average gestational age was 35.27 ± 3.35 weeks. There were 35 (62.5) preterm neonates and 31 (55.4) low birth weight newborns. 38 (67.9) had early-onset hypocalcaemia.

With 19 cases (33.9), maternal anaemia was the most common maternal relationship. Thirteen (23.2) had pregnancy-induced hypertension, and sixteen (28.6) had gestational diabetes mellitus. Prematurity and low birth weight were the most common newborn risk factors, followed by neonatal infection and birth asphyxia.

37 (66.1) had symptomatic hypocalcaemia. The most common symptom was jitteriness, which was followed by apnoea, poor eating, convulsions, and irritability. The average ionised calcium level was 0.874 ± 0.099 mmol/L. Ionised calcium and total blood calcium levels were much lower in newborns with symptoms than in those without. Neonatal infection and birth asphyxia demonstrated clinically significant relationships with borderline Fisher exact significance, but prematurity and male sex demonstrated substantial univariate connections with symptomatic hypocalcaemia. Prematurity, birth asphyxia, and male sex continued to be independent predictors in the adjusted logistic regression model.

The clinical profile and maternal-neonatal risk factors linked to ionised hypocalcaemia in newborns admitted to a tertiary care NICU were assessed in this study. The most prevalent newborn risk factor was prematurity (62.5%), which was followed by low birth weight (55.4%). Given that a significant amount of foetal calcium accretion takes place during the third trimester of pregnancy, these findings are biologically feasible. Therefore, transplacental calcium transport is disrupted by premature birth, which lowers calcium reserves and raises the risk of hypocalcaemia. Similarly, due to insufficient mineral reserves and related neonatal diseases, low birth weight babies are more susceptible to metabolic disorders. Maternal anaemia (33.9%) and gestational diabetes mellitus (28.6%) were the most commonly found correlations among maternal risk variables. One known risk factor for newborn hypocalcaemia is maternal diabetes.

It is thought to play a role through the newborn's altered calcium regulation and temporary functional hypoparathyroidism. Maternal anaemia may increase the risk of newborn hypocalcaemia by reflecting low maternal nutritional status and reduced foetal mineral accretion. In the current investigation, birth asphyxia (32.1%) and neonatal sepsis (39.3%) were frequently linked diseases. Monitoring calcium levels in severely unwell newborns is crucial since both diseases are known to disturb calcium homeostasis through inflammatory and metabolic pathways. These results confirm that newborns with serious perinatal and systemic diseases require greater attention. The most prevalent clinical symptom was jitteriness, which was followed by seizures and poor eating. Similar findings have been documented in earlier research, where the most common manifestation of newborn hypocalcaemia was neuromuscular irritability. The occurrence of seizures.

highlights the clinical importance of early detection and timely treatment in a significant percentage of neonates. This study's key conclusion was that newborns with symptoms had far lower ionised calcium levels than those without. Since ionised calcium is the physiologically active portion of serum calcium and has a stronger correlation with clinical symptoms than total serum calcium, this finding supports the usefulness of ionised calcium estimate. Ionised calcium is a more accurate diagnostic sign in severely unwell newborns since serum albumin levels and acid-base abnormalities might affect total calcium values. After receiving the proper care, most infants had positive results and were successfully discharged. Important strengths include the prospective study design, ionised calcium measurement, and investigation of maternal and neonatal risk variables.

Among neonates admitted to the NICU, ionised hypocalcaemia is a metabolic condition that is clinically relevant, especially in preterm and low birth weight babies. Birth asphyxia, neonatal sepsis, gestational diabetes mellitus, and maternal anaemia were frequently linked. The most common clinical symptom was jitteriness. Ionised calcium and total blood calcium levels were considerably lower in newborns with symptoms than in those without. In the adjusted model, symptomatic hypocalcaemia was independently predicted by male sex, prematurity, and birth asphyxia. Ionised calcium estimation-based targeted screening of high-risk newborns may promote early diagnosis, timely treatment, and better short-term neonatal outcomes.

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