Fetal Malnutrition: A Multicenter Cross-Sectional Study in Egypt

Introduction: Fetal malnutrition (FM) is a clinical condition resulting from failure of the fetus to acquire adequate amounts of subcutaneous fat and muscle mass during its intrauterine life, with short- and long-term implications. On the short term, FM is one of the leading causes of neonatal morbidities and mortalities worldwide (2.6 million deaths in 2016). Indeed, more than 80% of neonatal deaths occur among newborns of low birth weight (ascribed mainly to FM). On the long term, the Developmental Origins of Health and Disease (DOHaD) hypothesis asserts the relation between FM and various multisystemic adult chronic diseases through epigenetic mechanisms and fetal programming. This study addresses three aspects of FM. First, the prevalence of FM is estimated using the Clinical Assessment of Nutritional Status (CANS) score and its results are compared with anthropometric proportionality indices including the body mass index (BMI), the ponderal index (PI), and the mid-upper-arm circumference over head circumference (MUAC/HC) ratio. Second, the accuracies of the four methods are evaluated in the absence of a gold standard. Finally, the associations between FM and maternal, perinatal, and neonatal risk factors are statistically identified.

Materials and Methods: A multicenter cross-sectional study of full-term and preterm infants was conducted between November 2016 and October 2017 at the Cairo University and Al-Galaa Teaching Hospitals in Egypt. The study sample consisted of live born, singleton neonates of both genders with gestational ages of 28 to 40 weeks. The CANS score was evaluated for all infants enrolled in the study within 48 hours of birth. Moreover, BMI, PI, and MUAC/HC ratio were calculated, with FM cutoff values of CANS score  < 25, BMI  < 11.2 kg/m², PI  < 2.2 g/cm³, and MUAC/HC  < 0.27. Each of the four FM measures takes turns for the role of a reference method that arbitrarily replaces the necessarily missing gold standard. Detailed maternal and neonatal history was acquired (including perinatal circumstances, maternal illnesses, and nutritional intake during pregnancy).

Results: A total of 301 infants were enrolled in the study. Using the CANS score, BMI, PI, and MUAC/HC measures, the prevalence rate of FM for the studied population was 29.9, 23.26, 16.61, and 13.95%, respectively. [Table 1] lists the commonly used statistical indicators using all possible pairings of the FM diagnostic methods.

Conclusion: It is worthy to identify all newborns with FM timely and accurately after birth to provide effective preventive and curative interventions. Pronounced enhancement of FM detection could be achieved with combined use of BMI and the CANS score.

Keywords: fetal malnutrition, CANS score, anthropometric indices, prevalence, epigenetics, DOHaD

Table 1 Evaluation of four FM diagnostic method accuracies with each method taking turns for the role of the reference method

Fetal malnutrition diagnostic methods		Diagnostic accuracy measures				Error measures
Reference method	Assessed method	Sensitivity	Specificity	PPV	NPV	Type I error	Type II error	Total error
CANS score	CANS score	100	100	100	100	0	0	0
	BMI	62.22	93.36	80.00	85.28	4.65	11.30	15.95
	PI	46.67	96.21	84.00	80.88	2.66	15.95	18.60
	MUAC/HC	40.00	97.16	85.71	79.15	1.99	17.94	19.93
BMI	CANS score	80.00	85.28	62.22	93.36	11.30	4.65	15.95
	BMI	100	100	100	100	0	0	0
	PI	70.00	99.57	98	91.63	0.33	6.98	7.31
	MUAC/HC	48.57	96.54	80.95	86.10	2.66	11.96	14.62
PI	CANS score	84.00	80.88	46.67	96.21	15.95	2.66	18.60
	BMI	98.00	91.63	70.00	99.57	6.98	0.33	7.31
	PI	100	100	100	100	0	0	0
	MUAC/HC	54.00	94.02	64.29	91.12	4.98	7.64	12.62
MUAC/HC ratio	CANS score	85.71	79.15	40.00	97.16	17.94	1.99	19.93
	BMI	80.95	86.10	48.57	96.54	11.96	2.66	14.62
	PI	64.29	91.12	54.00	94.02	7.64	4.98	12.62
	MUAC/HC	100	100	100	100	0	0	0

Abbreviations: BMI, body mass index; CANS, clinical assessment of nutritional status; FM, fetal malnutrition; MUAC/HC, mid-upper-arm circumference over head circumference; NPV, negative predictive value; PI, ponderal index; PPV, positive predictive value.

Note: For completeness purposes, we include some obvious information (measures of a method with respect to itself) and some redundant information (when two methods interchange roles).