Precocious Puberty Diagnoses Spike, COVID-19 Pandemic, and Body Mass Index

Findings From a 4-year Study

Daniela Fava; Carlotta Pepino; Valentina Tosto; Roberto Gastaldi; Alessia Pepe; Dalila Paoloni; Marina Francesca Strati; Alessia Angelelli; Andrea Calandrino; Caterina Tedesco; Tiziana Camia; Anna Elsa Maria Allegri; Giuseppa Patti; Emilio Casalini; Marta Bassi; Maria Grazia Calevo; Flavia Napoli; Mohamad Maghnie

Disclosures

J Endo Soc. 2023;7(9)

Abstract and Introduction

Abstract

Context: Since the COVID-19 outbreak, the number of girls with suspected precocious puberty has increased.

Objective: To compare the incidence of idiopathic central precocious puberty (ICPP) during COVID-19 with that of the previous 4 years.

Methods: Anthropometric, biochemical, and radiological parameters were collected between January 2016 and June 2021 from 133 girls who met the Rapidly Progressive ICPP criteria (RP-ICPP).

Results: We found a higher incidence of RP-ICPP between March 2020 and June 2021 (group 2) compared with January 2016 through March 2020 (group 1) (53.5% vs 41.1%); 2021 showed the highest annual incidence (P < .05). Group 1 and group 2 differed in age at diagnosis (7.96 ± 0.71 vs 7.61 ± 0.94; P < .05), mean Tanner stage (2.86 ± 0.51 vs 2.64 ± 0; P < .05), and in the time between the appearance of thelarche and diagnosis (0.93 ± 0.75 vs 0.71 ± 0.62 years, P < .05). There was an increase in the number of girls aged <8 years in group 2 and a significantly higher number of girls aged >8 years was found in group 1 (42 in group 1 vs 20 in group 2, P < 0.05). Overall body mass index SD score showed higher values in group 2 (1.01 ± 1.23 vs 0.69 ± 1.15; P = .18), which spent an average of 1.94 ± 1.81 hours per day using electronic devices; 88.5% of this group stopped any physical activity.

Conclusions: A spike in new diagnoses of idiopathic (1.79-fold higher) and RP-CPP coincided with the COVID-19 pandemic. The incidence of RP-ICPP was 1.3-fold higher during COVID-19 with a trend toward an increase in body mass index SD score. The expanding use of digital devices and the reduction of daily physical activity represent possible risk factors.

Introduction

Over the past 2 years, the number of girls referred to pediatric endocrinologists for suspected precocious puberty (PP) increased significantly; this phenomenon was reported by many centers from different countries.^[1–11] Since early December 2019, COVID-19 has spread rapidly worldwide,^[12] and Italy was the first European country hit by the SARS-CoV-2 virus in the early months of 2020.^[12] The growing number of hospitalizations and deaths prompted the Council of Ministers to approve emergency measures for containment and prevention.^[13] From March to May 2020, the entire country underwent a total lockdown, resulting in a radical change in habits and family lifestyles, with serious impacts on children's lives. After the total lockdown, government measures continued, with closure of parks and gyms, until May 2021, leading to reduced social interaction and physical activities over a long period. Furthermore, distance learning and forced home breaks have had a significant impact on mental health^[14] and have promoted the adoption of inappropriate habits such as increased screen time, impaired sleep, and unhealthy food consumption.^[15,16]

The aim of the study is to evaluate the incidence of idiopathic central precocious puberty (ICPP) before and after the COVID 19 pandemic in Italy compared with the incidence of PP assessed over the previous 4 years and of a possible relationship between COVID-19 and pandemic-related lifestyle changes. We analyzed the anthropometric, biochemical, and radiological characteristics of girls diagnosed with rapidly progressive idiopathic precocious puberty during the COVID-19 pandemic compared with those who were diagnosed before the COVID-19 pandemic.

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Table 1. Demographic and anthropometric data of 133 girls diagnosed with rapidly progressive idiopathic central precocious puberty
	Group 1 n = 72	Group 2 n = 61	P value
Clinical/anamnestic data (mean ± SD)
Age at puberty onset (y)	7.03 ± 0.99	6.89 ± 0.99	.25
Age at GnRHa start (y)	7.96 ± 0.71	7.61 ± 0.94	.005
Delta age GnRHa start-puberty onset	0.93 ± 0.75	0.71 ± 0.62	.03
Height SDS	1.65 ± 1.15	1.37 ± 1.18	.21
BMI SDS	0.69 ± 1.15	1.01 ± 1.23	.18
Target height SDS	−0.20 ± 0.95	−0.26 ± 0.85	.74
Delta H-TH SDS	1.88 ± 0.99	1.67 ± 1.09	.26
Tanner stage	2.86 ± 0.51	2.64 ± 0.61	.02
Age at BA evaluation	7.94 ± 0.82	7.55 ± 0.96	.004
Bone age (BA)	9.75 ± 1.29	9.25 ± 1.48	.06
Delta CA-BA	1.80 ± 0.88	1.70 ± 1.02	.46
Age at V1^a	7.46 ± 0.74	7.33 ± 0.63	.29
BMI SDS at V1^a	0.62 ± 1.04	0.77 ± 1.49	.65
Delta BMI SDS (V2-V1)^a	−0.13 ± 0.51	0.12 ± 0.45	.15
Screen time (hours/day)	NA	1.94 ± 1.81
Familial history for CPP (number of patients)	16	12
Endocrine data (mean ± SD)
Baseline LH (U/L)	1.75 ± 2.24	1.26 ± 1.40	.56
LH peak (U/L)	16.22 ± 12.31	16.80 ± 13.17	.10
Baseline FSH (U/L)	4.36 ± 2.43	3.69 ± 2.00	.15
FSH peak (U/L)	11.99 ± 3.69	11.63 ± 3.82	.52
E2 (pg/mL)	19.49 ± 20.06	20.97 ± 22.54	.82
Metabolic data (mean ± SD)
Glycated hemoglobin (%)	5.02 ± 0.27	5.07 ± 0.27	.60
Baseline insulin (uU/mL)	13.34 ± 8.06	17.35 ± 14.22	.22
Triglycerides(mg/dL)	65.85 ± 36.96	67.43 ± 35.33	.61
Total cholesterol(mg/dL)	146.85 ± 24.36	150.62 ± 18.90	.40
HDL cholesterol (mg/dL)	54.91 ± 12.87	61.56 ± 12.21	.03
LDL cholesterol (mg/dL)	80.09 ± 18.10	84.78 ± 18.54	.15
Ultrasound data (mean ± SD)
Uterus length (mm)	37.09 ± 7.50	39.70 ± 8.62	.06
Uterus anteroposterior diameter (mm)	12.45 ± 3.38	11.59 ± 4.42	.08
Right ovary (cm³)	2.51 ± 1.67	2.20 ± 1.48	.25
Left ovary (cm³)	2.44 ± 1.36	2.47 ± 1.66	.69

Group 1: girls diagnosed between January 2016 and March 2020, before the COVID-19 pandemic; group 2: girls diagnosed between March 2020 and the end of June 2021, during the COVID-19 pandemic.
Abbreviations: BA, bone age; BMI, body mass index; CA, chronological age; CPP, central precocious puberty; E2, 17-beta estradiol; GnRHa, GnRH analog; HDL, high-density lipoprotein; H-TH, height-target height; LDL, low-density lipoprotein; NA, not available; SDS, SD score; V1, visit 1; V2, visit 2.
^aGirls diagnosed with slowly progressive idiopathic central precocious puberty at V1 (n = 27/72, 37.5% [group 1] vs n = 17/61, 27.9% [group 2]). All statistically significative P-values (<0.05) have been boldfaced.

Table 2. Mean BMI-SDS at GnRHa start according to chronological age and Tanner stage
Age at GNRHa start		BMI SDS (mean ± SD)
	N	Group 1	N	Group 2	P value
<6 y	n = 2	−0.05 ± 0.78	n = 4	−0.21 ± 0.36	NA
6–6.99 y	n = 4	0.77 ± 1.33	n = 7	1.88 ± 0.95	.11
7–7.99 y	n = 24	0.65 ± 1.17	n = 30	1.03 ± 1.22	.22
>8 y	n = 42	0.75 ± 1.15	n = 20	0.93 ± 1.27	.68
Tanner stage	BMI SDS (mean ± SD)
	N	Group 1	N	Group 2	P value
2	n = 15	0.44 ± 1.04	n = 26	0.85 ± 1.23	.38
3	n = 52	0.81 ± 1.16	n = 31	1.01 ± 1.19	.41
4	n = 5	0.25 ± 1.26	n = 4	2.07 ± 1.33	.06

Table 3. Demographic and anthropometric data of 106 European girls diagnosed with rapidly progressive idiopathic central precocious puberty
	Group 1 n = 60	Group 2 n = 46	P value
Clinical data (mean ± SD)
Age at puberty onset (y)	7.04 ± 1.06	6.93 ± 1.03	.38
Age at GnRHa start (y)	7.97 ± 0.74	7.60 ± 1.00	.01
Delta age GnRHa-puberty onset	0.93 ± 0.79	0.67 ± 0.50	.06
Height SDS	1.34 ± 0.08	1.31 ± 0.10	.27
Tanner stage	2.85 ± 0.48	2.63 ± 0.61	.03
Age at BA evaluation	7.95 ± 0.85	7.56 ± 1.04	.02
BMI SDS	0.61 ± 1.17	0.92 ± 1.20	.28
Target height SDS	−0.18 ± 0.88	−0.17 ± 0.76	.97
Delta H-TH SDS	1.77 ± 0.99	1.63 ± 0.95	.42
BA	9.70 ± 1.31	9.21 ± 1.60	.09
Delta CA-BA	1.76 ± 0.86	1.65 ± 1	.50
Age at V1^a	7.52 ± 0.74	7.27 ± 0.51	.06
BMI SDS at V1^a	0.62 ± 1.03	0.88 ± 1.61	.36
Delta BMI SDS (V2-V1)^a	−0.14 ± 0.55	0.07 ± 0.38	.29
Endocrine data (mean ± SD)
Baseline LH (U/L)	1.76 ± 2.16	1.28 ± 1.43	.53
LH peak (U/L)	16.28 ± 12.35	16.80 ± 11.24	.76
Baseline FSH (U/L)	4.33 ± 2.42	3.82 ± 2.10	.31
FSH peak (U/L)	11.99 ± 3.93	11.73 ± 3.86	.70
E2 (pg/mL)	20.38 ± 20.21	22.11 ± 24.05	.90
Metabolic data (mean ± SD)
Glycated hemoglobin (%)	5.01 ± 0.28	5.04 ± 0.29	.79
Baseline insulin (uU/mL)	12.55 ± 7.87	19.34 ± 15.73	.03
Triglycerides (mg/dL)	65.16 ± 39.03	66.70 ± 36.29	.70
Total cholesterol (mg/dL)	143.10 ± 24.56	149.50 ± 19.69	.16
HDL cholesterol (mg/dL)	53.26 ± 12.22	62.40 ± 12.53	.01
LDL cholesterol (mg/dL)	76.88 ± 17.26	83.16 ± 19.55	.08
Ultrasound data (mean ± SD)
Uterus length (mm)	37.22 ± 7.62	39.40 ± 9.18	.20
Uterus anteroposterior diameter (mm)	12.56 ± 3.52	11.55 ± 4.61	.09
Right ovary (cm³)	2.63 ± 1.76	2.29 ± 1.56	.31
Left ovary (cm³)	2.48 ± 1.32	2.50 ± 1.56	.75

Group 1: Girls diagnosed between January 2016 and March 2020, before Covid-19 pandemic; Group 2: Girls diagnosed between March 2020 and the end of June 2021, during Covid-19 pandemic;
Abbreviations: BA, bone age; BMI, body mass index; E2, 17-beta estradiol; GnRHa, GnRH analog; HDL, high-density lipoprotein; H-TH, height-target height; LDL, low-density lipoprotein; SDS, SD score; V1, visit 1; V2, visit 2.
^aGirls diagnosed as SP-ICPP at V1 (n = 26/60, 43,3% (Group1) vs n = 32/46, 69,6% (Group2)). All statistically significative P-values (<0.05) have been boldfaced.

Table 4. Demographic and anthropometric data of 27 extra-European girls diagnosed with rapidly progressive idiopathic central precocious puberty
	Group 1 n = 12	Group 2 n = 15	P value
Clinical data (mean ± SD)
Age at puberty onset (y)	7.00 ± 0.66	6.78 ± 0.85	.65
Age at GnRHa start (y)	7.95 ± 0.58	7.63 ± 0.73	.35
Delta age GnRHa-puberty onset	0.95 ± 0.60	0.85 ± 0.92	.28
Height SDS	1.79 ± 1.35	1.19 ± 1.70	.43
Tanner stage	2.92 ± 0.67	2.67 ± 0.62	.40
Age at BA evaluation	7.92 ± 0.67	7.51 ± 0.70	.08
BMI SDS	1.11 ± 0.95	1.28 ± 1.31	.40
Target height SDS	−0.35 ± 1.36	−0.56 ± 1.07	1
Delta H-TH SDS	2.51 ± 0.74	1.80 ± 1.52	.55
Bone age (BA)	9.83 ± 1.05	9.55 ± 1.24	.87
Delta CA-BA	1.88 ± 0.83	1.91 ± 1.14	.65
Age at V1^a	7.26 ± 0.76	7.52 ± 0.96	.56
BMI SDS at V1^a	0.63 ± 1.18	0.44 ± 1.21	.73
Delta BMI SDS (V2-V1)^a	−0.07 ± 0.37	0.27 ± 0.67	.56
Endocrine data (mean ± SD)
Baseline LH (U/L)	1.70 ± 2.72	1.20 ± 1.34	1
LH peak (U/L)	15.95 ± 12.77	16.81 ± 18.62	.48
Baseline FSH (U/L)	4.52 ± 2.61	3.31 ± 1.76	.24
FSH peak (U/L)	12.00 ± 2.53	11.32 ± 3.89	.63
E2 (pg/mL)	15.00 ± 19.47	17.21 ± 16.85	.63
Metabolic data (mean ± SD)
Glycated hemoglobin (%)	5.08 ± 0.21	5.13 ± 0.20	.78
Baseline insulin (uU/mL)	16.42 ± 8.50	11.37 ± 5.13	.16
Triglycerides (mg/dL)	69.00 ± 27.69	70.11 ± 33.45	.84
Total cholesterol (mg/dL)	164.71 ± 13.77	154.67 ± 16.04	.30
HDL cholesterol (mg/dL)	61.29 ± 14.29	58.67 ± 11.20	.92
LDL cholesterol (mg/dL)	92.00 ± 17.21	90.56 ± 13.78	.76
Ultrasound data (mean ± SD)
Uterus length (mm)	36.42 ± 7.18	40.64 ± 6.71	.14
Uterus anteroposterior diameter (mm)	11.91 ± 2.66	11.71 ± 3.91	.61
Right ovary (cm³)	1.94 ± 1.09	1.91 ± 1.25	.70
Left ovary (cm³)	2.23 ± 1.58	2.39 ± 2.00	.98

Group 1: girls diagnosed between January 2016 and March 2020, before the COVID-19 pandemic; group 2: girls diagnosed between March 2020 and the end of June 2021, during the COVID-19 pandemic.
Abbreviations: BA, bone age; BMI, body mass index; CA, chronological age; E2, 17-beta estradiol; GnRHa, GnRH analog; HDL, high-density lipoprotein; H-TH, height-target height; LDL, low-density lipoprotein; SDS, SD score; V1, visit 1; V2, visit 2.
^aGirls diagnosed with slowly progressive idiopathic central precocious puberty at V1 (n = 5/12, 41.6% [group 1] vs n = 4/15, 26.6% [group 2]).