Risk Factors for Nephrocalcinosis in Very Low Birth Weight Infants

Sang Eun Han; Teahyen Cha; Jinsup Kim; Ja Hye Kim; Chang Ryul Kim; Hyun Kyung Park; Hyun Ju Lee

doi:10.14734/PN.2019.30.2.14

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Han, Cha, Kim, Kim, Kim, Park, and Lee: Risk Factors for Nephrocalcinosis in Very Low Birth Weight Infants

Original Article

Perinatology 2019;30(1):14-19.

Published online: 20 March 2019

DOI: https://doi.org/10.14734/PN.2019.30.2.14

Risk Factors for Nephrocalcinosis in Very Low Birth Weight Infants

Sang Eun Han, MD, Teahyen Cha, MD, Jinsup Kim, MD, Ja Hye Kim, MD, Chang Ryul Kim, MD, Hyun Kyung Park, MD, Hyun Ju Lee, MD

Department of Pediatrics, Hanyang University College of Medicine, Seoul, Korea

Correspondence to Hyun Ju Lee, MD Department of Pediatrics, Hanyang University College of Medicine, 222-1 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea Tel: +82-2-2290-8397 Fax: +82-2-2297-2380 E-mail: blesslee77@hanmail.net

Received 24 May 2018 Revised 23 June 2018 Accepted 23 June 2018

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

The objective was to identify risk factors for nephrocalcinosis in very low birth weight (VLBW) infants.

Methods

Prospective study has done between 2014 and 2017. The study included 81 VLBW infants in the neonatal intensive care unit (NICU). Renal ultrasonography was performed at four weeks and 3 months. Baseline characteristics, complications and medication during NICU admission were collected. 25-(OH)-vitamin D, calcium, phosphorous, alkaline phosphatase, urine calcium to creatinine ratio were serially measured.

Results

The incidence of nephrocalcinosis was 16.9%. On univariate analysis, gestational age, lower birth weight, maternal pregnancy-induced hypertension, neonatal sepsis, and frequency of vancomycin and caffeine citrate treatment were significantly associated with nephrocalcinosis. In addition, preterm infants with nephrocalcinosis had lower cord blood 25-(OH)-vitamin D and serum calcium levels and higher serum alkaline phosphatase levels at 2 weeks of life. Multivariate analysis showed that gestational age (P=0.042), birth weight (P=0.019), sepsis (P=0.046), small for gestational age (P=0.015), and maternal pregnancy-induced hypertension (P=0.024) were significant risk factors for nephrocalcinosis.

Conclusion

This study suggests that neonatal sepsis and maternal pregnancy-induced hypertension, in addition to gestational age and birth weight are important perinatal risk factors for nephrocalcinosis.

Keywords: Nephrocalcinosis, Prematurity, Very low birth weight, Risk factors

References

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Table 1.

Baseline Characteristics

	Non-NC group (n=68)	NC group (n=13)	P-value
Gestational age (weeks)	27.6±2.5	26.1±2.0	0.047
Birth weight (g)	1,005.2±265.4	807.7±232.7	0.018
SGA	5 (7.25)	4 (30.77)	0.048
Male	35 (51.47)	7 (53.85)	1.000
Born from April to October	33 (48.53)	8 (61.54)	0.578
Mother age	33.4±4.0	35.9±4.4	0.071
Histologic chorioamnionitis	47 (69.12)	8 (61.54)	0.832
Antenatal steroid	51 (75)	9 (69.23)	0.679
Apgar 5 minutes (score)	5.6±1.6	5.6±1.1	0.958
Ponderal index	2.3±0.3	2.5±0.5	0.163
GDM	8 (11.76)	0 (0)	0.426
PIH	3 (4.41)	4 (30.77)	0.010
Duration of hospitalization (days)	88.3±36.6	113.3±54.1	0.027
pH of the first blood gas test of the life	7.21±0.09	7.20±0.14	0.893

Values are presented as mean±standard deviation or number (%). Abbreviations: NC, nephrocalcinosis; SGA, small for gestational age; GDM, gestational diabetes mellitus; PIH, pregnancy- induced hypertension.

Table 2.

Complications and Medications during NICU Admission

	Non-NC group (n=68)	NC group (n=13)	P-value
RDS	63 (92.65)	13 (100)	0.704
PDA ligation	31 (45.59)	8 (61.43)	0.452
Moderate BPD or higher	27 (39.71)	7 (53.85)	0.522
Culture proven sepsis NEC grade II or higher	27 (39.71) 4 (5.88)	10 (76.92) 2 (15.38)	0.030 0.245
IVH, all grade	32 (47.06)	8 (61.43)	0.513
ROP	25 (36.76)	6 (46.15)	0.744
Duration of mechanical ventilat	tion 23.1±17.2	30.7±14.8	0.083
(days)
Total TPN day (days)	44.3±22.4	55.2±23.8	0.146
Aminoglycoside	65/66 (98.45)	13 (100)	0.835
Aminoglycoside (days)	2.8±1.0	3.6±2.5	0.790
Vancomycin	38/66 (57.58)	11 (84.62)	0.060
Vancomycin (days)	9.6±10.3	16.8±14.6	0.049
Caffeine citrate	62/66 (93.94)	13 (100)	0.480
Caffeine citrate (days)	59.3±25.58	83.9±10.0	<0.001
Ibuprofen	33/66 (50)	6 (46.15)	0.520
Ibuprofen (days)	2.1±2.7	1.7±2.8	0.634
Dexamethasone	23/66 (34.85)	5 (38.46)	0.519
Dexamethasone (days)	4.8±6.5	4.5±6.1	0.960
Furosemide	35/66 (53.03)	4 (30.77)	0.122
Furosemide (days)	1.9±2.6	2.3±3.1	0.934
Thiazide	40/66 (60.60)	6/13 (46.15)	0.740
Thiazide (day)	10.6±16.9	12.2±18.5	0.677
Surfactant	61/66 (94.42)	13 (100)	0.397
Surfactant (days)	2.2±1.5	2.9±1.4	0.067
Elemental calcium in TPN	25.1±8.1	27.4±6.9	0.483
(mg/kg/day)

Values are presented as mean±standard deviation or number (%). Abbreviations: NC, nephrocalcinosis; RDS, respiratory distress syndrome; PDA, patent ductus arteriosus; BPD, bronchopulmonary dysplasia; NEC, necrotizing enterocolitis; IVH, intraventricular hemorrhage; ROP, retinopathy of prematurity; TPN, total parenteral nutrition.

Table 3.

Laboratory Findings on Cord blood, 2nd Weeks, 6th Weeks, 12th Weeks of Life

	Non-NC group (n=68)	NC group (n=13)	P-value
Calcium in cord blood (mg/dL)	7.27±0.89	7.02±1.12	0.468
Serum calcium at 2nd weeks of life	9.42±0.71	9.21±1.37	0.605
(mg/dL)
Serum calcium at 6th weeks of life	9.64±0.71	8.99±0.73	0.013
(mg/dL)
Serum calcium at 12th weeks of life	9.65±0.55	9.67±0.54	0.876
(mg/dL)
Vitamin D in cord blood (ng/mL)	21.31±14.98	16.26±7.80	0.022
Serum vitamin D at 2nd weeks of life	e 20.60±9.95	19.81±67.74	0.199
(ng/mL)
Serum vitamin D at 6th weeks of life	24.84±9.84	20.88±4.62	0.086
(ng/mL)
Serum vitamin D at 12th weeks of	45.43±21.91	39.89±19.06	0.097
life (ng/mL)
Phosphorus in cord blood (mg/dL)	4.93±1.26	4.65±1.44	0.567
Serum phosphorus at 2nd weeks of	5.17±2.01	4.35±1.29	0.109
life (mg/dL)
Serum phosphorus at 6th weeks of	5.60±1.16	5.30±1.25	0.489
life (mg/dL)
Serum phosphorus at 12th weeks of	6.08±0.83	5.96±0.86	0.687
life (mg/dL)
ALP in cord blood (U/L)	196.61±58.14	229.92±141.32	0.158
Serum ALP at 2nd weeks of life (U/L)	) 398.02±154.00	532.50±290.10	0.021
Serum ALP at 6th weeks of life (U/L)	389.62±130.24	485.58±185.23	0.035
Serum ALP at 12th weeks of life(U/L)	) 320.34±108.02	357.54±112.84	0.063
Uca/cr at PMA 32 weeks of life	0.20±0.20	0.27±0.26	0.391

Values are presented as mean±standard deviation. Abbreviations: NC, nephrocalcinosis; ALP, Alkaline phosphatase; Uca/cr, random urinary calcium/creatinine ratio; PMA, postmesntural age.

Table 4.

Significance of Risk Factors by Multivariate Analysis

	P-value	OR	95% CI
Gestational age	0.042	0.836	0.704–0.993
Birth weight	0.019	1.011	1.002–1.021
Culture proven sepsis	0.046	0.068	0.004–1.068
SGA	0.015	0.004	0.000–0.331
PIH	0.024	0.001	0.000–0.403
Duration of vancomycin usage	0.843	1.009	0.926–1.098
Duration of Caffeine citrate usage	0.053	1.125	0.998–1.269

Abbreviations: OR, odds ratio; CI, confidence interval; SGA, small for gestational age; PIH, pregancy induced hypertension.

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