Prediction of Perinatal and Neurodevelopmental Outcomes in Newborns with a Birth Weight below the 3rd Percentile: Performance of Two International Curves – Prospective Cohort from a Brazilian City

Okido, Marcos Masaru; Cavalli, Ricardo de Carvalho; Cardoso, Viviane Cunha; Marcolin, Alessandra Cristina

doi:10.1055/s-0043-1770131

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Revista Brasileira de Ginecologia e Obstetrícia

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Original Article • Rev Bras Ginecol Obstet. 45 (5) • 2023 • https://doi.org/10.1055/s-0043-1770131 copy

Prediction of Perinatal and Neurodevelopmental Outcomes in Newborns with a Birth Weight below the 3rd Percentile: Performance of Two International Curves – Prospective Cohort from a Brazilian City

Predição de resultados perinatais e de neurodesenvolvimento em recém-nascidos com peso ao nascer abaixo do percentil 3: Desempenho de duas curvas internacionais – coorte prospectiva de uma cidade brasileira

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objectives

To evaluate the performance of Intergrowth-21 st (INT) and Fetal Medicine Foundation (FMF) curves in predicting perinatal and neurodevelopmental outcomes in newborns weighing below the 3rd percentile.

Methods

Pregnant women with a single fetus aged less than 20 weeks from a general population in non-hospital health units were included. Their children were evaluated at birth and in the second or third years of life. Newborns (NB) had their weight percentiles calculated for both curves. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV), and area under the ROC curve (ROC-AUC) for perinatal outcomes and neurodevelopmental delay were calculated using birth weight < 3rd percentile as the cutoff.

Results

A total of 967 children were evaluated. Gestational age at birth was 39.3 (± 3.6) weeks and birth weight was 3,215.0 (± 588.0) g. INT and FMF classified 19 (2.4%) and 49 (5.7%) newborns below the 3rd percentile, respectively. The prevalence of preterm birth, tracheal intubation >24 hours in the first three months of life, 5th minute Apgar <7, admission to a neonatal care unit (NICU admission), cesarean section rate, and the neurodevelopmental delay was 9.3%, 3.3%, 1.3%, 5.9%, 38.9%, and 7.3% respectively. In general, the 3rd percentile of both curves showed low sensitivity and PPV and high specificity and NPV. The 3rd percentile of FMF showed superior sensitivity for preterm birth, NICU admission, and cesarean section rate. INT was more specific for all outcomes and presented a higher PPV for the neurodevelopmental delay. However, except for a slight difference in the prediction of preterm birth in favor of INT, the ROC curves showed no differences in the prediction of perinatal and neurodevelopmental outcomes.

Conclusion

Birth weight below the 3rd percentile according to INT or FMF alone was insufficient for a good diagnostic performance of perinatal and neurodevelopmental outcomes. The analyzes performed could not show that one curve is better than the other in our population. INT may have an advantage in resource contingency scenarios as it discriminates fewer NB below the 3rd percentile without increasing adverse outcomes.

Keywords
fetal growth retardation; birth weight; neurodevelopmental disorders

	Total n = 967	INT NB weight p < 3 n = 19	FMF NB weight p < 3 n = 49	p-value^d
Maternal age, years (IQR)	26.0 (12.0)	26.0 (12.0)	26.0 (12.0)	0.718
BMI, kg/m²2 Sacchi C, Marino C, Nosarti C, Vieno A, Visentin S, Simonelli A. Association of intrauterine growth restriction and small for gestational age status with childhood cognitive outcomes: a systematic review and meta-analysis. JAMA Pediatr. 2020;174 (08):772–781. Doi: 10.1001/jamapediatrics.2020.1097 https://doi.org/10.1001/jamapediatrics.2... (IQR)	26.5 (6.8)	27.8 (8.5)	27.0 (6.6)	0.218
Study US, weeks IQR)	22.9 (1.7)	23.1 (2.3)	22.9 (1.7)	0.919
Ethnicity
- White (%)	510 (52.4)	11 (57.9)	27 (55.1)	0.756
- Non-white (%)	457 (47.3)	8 (42.1)	22 (44.9)
Schooling
- ≥ 12 years (%)	77 (8.0)	1 (5.3)	4 (8.2)	0.595
- < 12 years (%)	890 (92.0)	18 (94.7)	45 (91.8)
Marital status
- Married or cohabiting (%)	778 (80.5)	14 (73.7)	37 (75.5)	0.810
- No partner (%)	189 (19.5)	5 (26.3)	12 (24.5)
Parity
- 0–1 (%)	773 (79.9)	16 (84.2)	43 (87.8)	0.515
- ≥2 (%)	194 (19.5)	3 (15.8)	6 (12.2)
NB sex
- Male (%)	474(49.0)	11 (57.9)	23 (46.9)	0.228
- Female (%)	493 (51.9)	8 (42.1)	26 (53.1)
Hypertension^a a Types of hypertension included chronic, gestational, or preeclampsia. Types of diabetes included: type 1, 2 our gestational; bAny amount of consumption; cChild’s age at evaluation of neurodevelopment by Bayley III test; dComparisons of categorical and numerical variables considering only newborns with <p3 in each curve, through GEE (Generalized Estimating Equations) analysis; en = 877; fn = 90; gn = 13; hn = 6; in = 37; jn = 12. (%)	149 (15.4)	4 (21.1)	12 (24.5)	0.667
Diabetes^a a Types of hypertension included chronic, gestational, or preeclampsia. Types of diabetes included: type 1, 2 our gestational; bAny amount of consumption; cChild’s age at evaluation of neurodevelopment by Bayley III test; dComparisons of categorical and numerical variables considering only newborns with <p3 in each curve, through GEE (Generalized Estimating Equations) analysis; en = 877; fn = 90; gn = 13; hn = 6; in = 37; jn = 12. (%)	59 (6.1)	2 (10.5)	2 (4.1)	< 0.001
Smoking^b (%)	120 (12.4)	6 (31.6)	11 (22.5)	0.189
Alcohol^b (%)	238 (24.6)	6 (31.6)	14 (28.6)	0.706
Delivery, weeks (IQR)	39.3 (3.6)	39.6 (4.6)	39.3 (3.4)	0.220
≥ 37 weeks	39.4 (1.7)^e	40.0 (1.6)^g	39.7 (1.4)ⁱ
< 37 weeks	35.7 (2.4)^f	35.9 (1.0)^h	34.8 (2.3)^j
NB weight, g (IQR)	3215.0 (588.0)	2425.0 (660.0)	2455.0 (465.0)	0.464
≥37 weeks	3250.0 (570)^e	2500.0 (135)^g	2500.0 (295)ⁱ
< 37 weeks	2645.0 (877.5)^f	1842.5 (178.8)^h	1735.0 (381.3)^j
Breastfeeding ≥ 1month (%)	863 (89.3)	18 (94.7)	41 (83.7)	0.187
Day care center (%)	469 (48.5)	4 (21.1)	12 (24.5)	0.667
Neurodevelop. Assessm^c, years (IQR)	1.9 (0.3)	1.8 (0.3)	1.8 (0.3)	0.428

		n (%)	Sensitivity% (95%CI)	p-value^a	Specificity% (95%CI)	p-value^a	PPV (95%CI)	p-value^b	NPV (95% CI)	p-value^b
Preterm birth n = 90 (9.3%)	INT	6 (31.6%)	6.7 (2.7–14.5)	0.014	98.5 (97.4–99.2)	<0.001	31.6 (13.6–56.5)	0.334	91.1 (89.1–92.8)	0.136
Preterm birth n = 90 (9.3%)	FMF	12 (24.5%)	13.3 (7.4–22.5)		95.8 (94.2–97.0)		24.5 (13.8–39.2)			91.5 (89.5–93.2)
Intubation n = 32 (3.3%)	INT	2 (10.5%)	6.3 (1.1–22.2)	0.083	98.2 (97.0–98.9)	<0.001	10.5 (1.8–34.5)	0.952	96.8 (95.5–97.8)	0.217
Intubation n = 32 (3.3%)	FMF	5 (10.2%)	15.6 (5.9–33.6)		95.3 (93.7–96.5)		10.2 (3.8–23.0)			97.1 (95.7–98.0)
5 minute Apgar <7 n = 13 (1.3%)	INT	0	0.0 (0.0–28.4)	0.317	98.0 (96.8–98.8)	<0.001	0.0 (0.0–20.9)	1.00	98.6 (97.6–99.2)	0.537
5 minute Apgar <7 n = 13 (1.3%)	FMF	1 (2.0%)	7.7 (0.4–37.9)		95.1 (93.4–96.3)		2.1 (0.1–12.5)			98.7 (97.7–99.3)
NICU admission n = 58 (5.9%)	INT	2 (10.5%)	3.5 (0.6–13.0)	0.014	98.1 (97.0–98.9)	<0.001	10.5 (1.8–34.5)	0.429	94.1 (92.4–95.5)	0.065
NICU admission n = 58 (5.9%)	FMF	8 (16.3%)	13.8 (6.6–25.9)		95.5 (93.9–96.7)		16.3 (7.8–30.2)			94.6 (92.8–95.9)
Cesarean n = 376 (38.9%)	INT	8 (42.1%)	2.1 (1.0–4.3)	<0.001	98.1 (96.6–99.0)	<0.001	42.1 (21.1–66.0)	0.327	61.2 (58.0–64.3)	0.060
Cesarean n = 376 (38.9%)	FMF	17 (34.7%)	6.7 (4.4–9.8)		95.9 (93.9–97.3)		51.0 (36.5–65.4)			61.8 (58.5–64.9)
Neurodevelopment n = 71 (7.3%)	INT	4 (21.1%)	5.6 (1.8–14.5)	0.317	98.3 (97.2–99.0)	<0.001	21.1 (7.0–46.1)	0.005	92.9 (91.1–94.4)	0.257
Neurodevelopment n = 71 (7.3%)	FMF	5 (10.2%)	7.0 (2.6–16.4)		95.1 (93.4–96.4)		10.2 (3.8–23.0)			92.8 (90.9–94.4)

	INT	FMF	p-value
	ROC curve AUC (95%CI)	ROC curve AUC (95%CI)	p-value
Preterm birth	0.54 (0.47–0.60)	0.52 (0.45–0.59)	0.032
Intubation	0.57 (0.48–0.67)	0.60 (0.49–0.70)	0.090
5 minute Apgar <7	0,54 (0.39–0.70)	0.56 (0.39–0.73)	0.437
NICU admission	0.58 (0.50–0.66)	0.59 (0.51–0.67)	0.319
Cesarean	0.57 (0.53–0.60)	0.56 (0.53–0.60)	0.887
Neurodevelopment	0.52 (0.45–0.59)	0.52 (0.45–0.59)	0.453

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[1] Address for correspondence Marcos Masaru Okido, Avenida dos Bandeirantes, 3900, 14049-900, Monte Alegre, Ribeirão Preto, SP, Brazil (e-mail: mokido@hcrp.usp.br).