Association Between Serum Ferritin Concentration and Risk of Adverse Maternal and Fetal Pregnancy Outcomes: A Retrospective Cohort Study

Figures & data

Table 1 Baseline Characteristics of Participants According to Quartiles of SF at 16–18th Weeks of Gestation

Characteristic	Total	SF at 16–18th Weeks of Gestation (ug/L)				P value
		Quartile 1 <18.32	Quartile 2 18.32–31.34	Quartile 3 31.34–55.90	Quartile 4 >55.90
Number of cases	2327	584	580	583	580
Maternal characteristic
Maternal age (years)	31.0 (29.0, 35.0)	31.0 (29.0, 34.0)	32.0 (29.0, 35.0)	32.0 (29.0, 34.0)	31.0 (29.0, 35.0)	0.365
BMI (kg/m^2)	20.5 (18.8, 22.3)	20.4 (18.8, 22.1)	20.4 (18.8, 22.2)	20.6 (19.0, 22.3)	20.6 (18.8, 22.5)	0.634
BMI categories						0.527
< 24.0 (n, %)	2057 (88.4%)	526 (90.1%)	508 (87.6%)	514 (88.2%)	509 (87.8%)
≥24.0 (n, %)	270 (11.6%)	58 (9.9%)	72 (12.4%)	69 (11.8%)	71 (12.2%)
Education background						0.477
Primary (n, %)	5 (0.2%)	2 (0.3%)	1 (0.2%)	0 (0.0%)	2 (0.3%)
Secondary (n, %)	488 (21.0%)	131 (22.5%)	130 (22.4%)	114 (19.6%)	113 (19.5%)
College and above (n, %)	1834 (78.8%)	451 (77.2%)	449 (77.4%)	469 (80.4%)	465 (80.2%)
Smoking status (n, %)	6 (0.3%)	1 (0.2%)	2 (0.3%)	0 (0.0%)	3 (0.5%)	0.237
Alcohol consumption status (n, %)	7 (0.3%)	5 (0.9%)	2 (0.3%)	0 (0.0%)	0 (0.0%)	0.018
Conception method (n, %)						0.939
Natural	2308 (99.2%)	578 (99.0%)	576 (99.3%)	579 (99.3%)	575 (99.1%)
Artificial	19 (0.8%)	6 (1.0%)	4 (0.7%)	4 (0.7%)	5 (0.9%)
Parity						0.469
Nulliparity (n, %)	1724 (74.1%)	441 (75.5%)	416 (71.7%)	437 (75.0%)	430 (74.1%)
Multipara (n, %)	603 (25.9%)	143 (24.5%)	164 (28.3%)	146 (25.0%)	150 (25.9%)
Abortion history (n, %)	745 (32.0%)	178 (30.5%)	192 (33.1%)	182 (31.2%)	193 (33.3%)	0.673
Thalassemia history (n, %)	127 (5.5%)	34 (5.8%)	35 (6.0%)	28 (4.8%)	30 (5.2%)	0.777
Gestational age at delivery (weeks)	39.0 (38.0, 40.0)	39.0 (38.0, 40.0)	39.0 (38.0, 40.0)	39.0 (38.0, 40.0)	39.0 (38.0, 40.0)	0.873
SF at 16–18th weeks of gestation (μg/L)	31.3 (18.3, 55.9)	12.2 (9.3, 14.7)	24.2 (21.0, 27.8)	42.0 (36.3, 48.3)	82.6 (62.3, 113.1)	< 0.001
SF at 28–32th weeks of gestation (μg/L)	23.9 (16.0, 32.7)	21.7 (14.9, 31.0)	23.0 (14.7, 30.6)	24.6 (16.6, 33.5)	26.6 (18.6, 35.9)	< 0.001
Hemoglobin (g/L)	116.0 (111.0, 122.0)	114.2 (108.0, 120.0)	118.0 (111.5, 123.0)	117.0 (112.0, 123.0)	116.0 (111.0, 123.0)	< 0.001
Glucose metabolism
Fasting blood glucose (mmol/l)	4.6 (4.4, 4.8)	4.5 (4.4, 4.7)	4.6 (4.4, 4.7)	4.5 (4.4, 4.8)	4.5 (4.3, 4.8)	0.798
1-h post-load glucose (mmol/l)	8.0 (7.0, 9.2)	8.0 (6.9, 9.1)	8.0 (7.0, 9.2)	7.8 (6.8, 9.0)	8.2 (7.0, 9.3)	0.028
2-h post-load glucose (mmol/l)	6.9 (6.1, 7.8)	6.9 (6.1, 7.8)	6.9 (6.1, 7.9)	6.8 (6.0, 7.7)	7.0 (6.2, 7.9)	0.027
Newborn characteristics
Sex						0.171
Female (n, %)	1085 (46.6%)	252 (43.2%)	288 (49.7%)	274 (47.1%)	271 (46.7%)
Male (n, %)	1241 (53.4%)	332 (56.8%)	292 (50.3%)	308 (52.9%)	309 (53.3%)
Birth weight (g)	3300.0 (3000.0, 3550.0)	3300.0 (3035.0, 3600.0)	3250.0 (3007.5, 3550.0)	3250.0 (3000.0, 3550.0)	3250.0 (2955.0, 3500.0)	0.055
Birth length (cm)	50.0 (49.0, 51.0)	50.0 (49.0, 51.0)	50.0 (49.0, 51.0)	50.0 (49.0, 51.0)	50.0 (49.0, 51.0)	0.101
Head circumference (cm)	34.0 (33.0, 35.0)	34.0 (33.0, 35.0)	34.0 (33.0, 35.0)	34.0 (33.0, 35.0)	34.0 (33.0, 35.0)	0.114
Chest circumference (cm)	33.0 (32.0, 34.0)	33.0 (32.0, 34.8)	33.0 (32.0, 34.0)	33.0 (32.0, 34.0)	33.0 (32.0, 34.0)	0.516
Adverse maternal and fetal outcomes
GDM (n, %)	534 (22.9%)	120 (20.5%)	130 (22.4%)	125 (21.4%)	159 (27.4%)	0.026
Premature birth (n, %)	116 (5.0%)	27 (4.6%)	29 (5.0%)	28 (4.8%)	32 (5.5%)	0.903
Macrosomia (n, %)	86 (3.7%)	25 (4.3%)	17 (2.9%)	23 (3.9%)	21 (3.6%)	0.659
LBW (n, %)	96 (4.1%)	23 (3.9%)	26 (4.5%)	22 (3.8%)	25 (4.3%)	0.926
LGA (n, %)	270 (11.6%)	72 (12.3%)	64 (11.0%)	73 (12.5%)	61 (10.5%)	0.654
SGA (n, %)	166 (7.1%)	35 (6.0%)	34 (5.9%)	40 (6.9%)	57 (9.8%)	0.029
Tall stature at birth	124 (5.3%)	32 (5.5%)	25 (4.3%)	34 (5.8%)	33 (5.7%)	0.646
Short stature at birth	96 (4.1%)	30 (5.1%)	18 (3.1%)	27 (4.6%)	21 (3.6%)	0.285
Big head circumference	317 (13.6%)	86 (14.7%)	66 (11.4%)	96 (16.5%)	69 (11.9%)	0.036
Small head circumference	93 (4.0%)	16 (2.7%)	16 (2.8%)	30 (5.1%)	31 (5.3%)	0.024

Notes: Data were expressed as the median (quartiles) for continuous variables and as n (%) for categorical variables. P values for continuous variables were determined by Kruskal–Wallis test and categorical variables were determined by chi-square test.

Abbreviations: SF, serum ferritin; BMI, body mass index; GDM, gestational diabetes mellitus; LBW, low birth weight; LGA, large for gestational age; SGA, small for gestational age.

Table 2 Odds Ratios (95% Confidence Intervals) for the Occurrence of GDM According to the SF at 16–18th Weeks of Gestation

	SF at 16–18th Weeks of Gestation (ug/L)				P Trend	Per-SD Increase
	Quartile 1 <18.32	Quartile 2 18.32–31.34	Quartile 3 31.34–55.90	Quartile 4 >55.90
n (%)	120 (20.5%)	130 (22.4%)	125 (21.4%)	159 (27.4%)
OR (95% CI)	1.00 (ref)	1.12 (0.84–1.48)	1.06 (0.80–1.40)	1.46 (1.11–1.92)	0.026	1.15 (1.05–1.26)
AOR (95% CI)
Model 1	1.00 (ref)	1.06 (0.80–1.41)	1.02 (0.77–1.36)	1.45 (1.10–1.91)	0.022	1.16 (1.06–1.27)
Model 2	1.00 (ref)	1.05 (0.79–1.40)	1.01 (0.76–1.35)	1.43 (1.09–1.89)	0.025	1.16 (1.05–1.27)

Notes: Model 1 adjusted for age, BMI. Model 2 adjusted for the variables in Model 1 plus education background, smoking status, alcohol consumption status, conception method, parity, abortion history, thalassemia history and hemoglobin.

Abbreviations: SF, serum ferritin; GDM, gestational diabetes mellitus, OR odds ratio, AOR, adjusted odds ratio.

Table 3 Odds Ratios (95% Confidence Intervals) for the Occurrence of Adverse Maternal and Fetal Outcomes According to the SF at 16–18th Weeks of Gestation

Outcomes	SF at 16–18th Weeks of Gestation (ug/L)				P Trend	Per-SD Increase
	Quartile 1 <18.32	Quartile 2 18.32–31.34	Quartile 3 31.34–55.90	Quartile 4 >55.90
N	584	580	583	580
Premature birth
Rate (%)	27 (4.6%)	29 (5.0%)	28 (4.8%)	32 (5.5%)	0.903
OR (95% CI)	1.00 (ref)	1.09 (0.63–1.86)	1.04 (0.61–1.79)	1.21 (0.71–2.04)	0.908	1.04 (0.87–1.25)
AOR (95% CI)	1.00 (ref)	1.10 (0.64–1.89)	1.07 (0.62–1.85)	1.26 (0.74–2.14)	0.853	1.06 (0.89–1.27)
Macrosomia
Rate (%)	25 (4.3%)	17 (2.9%)	23 (3.9%)	21 (3.6%)	0.659
OR (95% CI)	1.00 (ref)	0.68 (0.37–1.26)	0.92 (0.52–1.64)	0.84 (0.47–1.52)	0.657	1.04 (0.85–1.28)
AOR (95% CI)	1.00 (ref)	0.67 (0.35–1.26)	0.91 (0.51–1.64)	0.84 (0.46–1.52)	0.643	1.04 (0.85–1.27)
LBW
Rate (%)	23 (3.9%)	26 (4.5%)	22 (3.8%)	25 (4.3%)	0.926
OR (95% CI)	1.00 (ref)	1.15 (0.65–2.03)	0.96 (0.53–1.74)	1.10 (0.62–1.96)	0.925	1.06 (0.88–1.29)
AOR (95% CI)	1.00 (ref)	1.21 (0.68–2.16)	1.02 (0.56–1.86)	1.17 (0.65–2.09)	0.892	1.08 (0.89–1.30)
LGA
Rate (%)	72 (12.3%)	64 (11.0%)	73 (12.5%)	61 (10.5%)	0.654
OR (95% CI)	1.00 (ref)	0.88 (0.62–1.26)	1.02 (0.72–1.44)	0.84 (0.58–1.20)	0.654	0.95 (0.83–1.09)
AOR (95% CI)	1.00 (ref)	0.84 (0.58–1.21)	0.99 (0.69–1.42)	0.81 (0.56–1.18)	0.557	0.94 (0.82–1.08)
SGA
Rate (%)	35 (6.0%)	34 (5.9%)	40 (6.9%)	57 (9.8%)	0.029
OR (95% CI)	1.00 (ref)	0.98 (0.60–1.59)	1.16 (0.72–1.85)	1.71 (1.10–2.65)	0.032	1.21 (1.07–1.38)
AOR (95% CI)	1.00 (ref)	1.06 (0.65–1.73)	1.22 (0.76–1.97)	1.79 (1.15–2.79)	0.032	1.21 (1.06–1.38)

Notes: Logistic regression models were adjusted for age, BMI, education background, smoking status, alcohol consumption status, conception method, parity, abortion history, thalassemia history and hemoglobin.

Abbreviations: SF, serum ferritin; LBW, low birth weight; LGA, large for gestational age; SGA, small for gestational age; OR odds ratio; AOR, adjusted odds ratio.

Table 4 Odds Ratios (95% Confidence Intervals) for the Occurrence of Adverse Maternal and Fetal Outcomes According to the SF at 28–32th Weeks of Gestation

Outcomes	SF at 28–32th Weeks of Gestation (ug/L)				P Trend	Per-SD Increase
	Quartile 1 <16.01	Quartile 2 16.01–23.91	Quartile 3 23.91–32.71	Quartile 4 >32.71
N	582	582	582	581
Premature birth
Rate (%)	25 (4.3%)	31 (5.3%)	33 (5.7%)	27 (4.6%)	0.692
OR (95% CI)	1.00 (ref)	1.25 (0.73–2.15)	1.34 (0.79–2.28)	1.09 (0.62–1.89)	0.697	1.02 (0.85–1.22)
AOR (95% CI)	1.00 (ref)	1.21 (0.70–2.09)	1.31 (0.77–2.25)	1.05 (0.60–1.85)	0.730	1.01 (0.84–1.22)
Macrosomia
Rate (%)	27 (4.6%)	25 (4.3%)	22 (3.8%)	12 (2.1%)	0.090
OR (95% CI)	1.00 (ref)	0.92 (0.53–1.61)	0.81 (0.45–1.44)	0.43 (0.22–0.86)	0.106	0.70 (0.53–0.94)
AOR (95% CI)	1.00 (ref)	0.87 (0.49–1.53)	0.76 (0.42–1.36)	0.42 (0.21–0.84)	0.096	0.69 (0.51–0.93)
LBW
Rate (%)	17 (2.9%)	28 (4.8%)	28 (4.8%)	23 (4.0%)	0.319
OR (95% CI)	1.00 (ref)	1.68 (0.91–3.10)	1.68 (0.91–3.10)	1.37 (0.72–2.59)	0.321	1.06 (0.88–1.28)
AOR (95% CI)	1.00 (ref)	1.71 (0.92–3.18)	1.75 (0.94–3.25)	1.41 (0.74–2.69)	0.282	1.06 (0.88–1.28)
LGA
Rate (%)	70 (12.0%)	64 (11.0%)	70 (12.0%)	66 (11.4%)	0.933
OR (95% CI)	1.00 (ref)	0.90 (0.63–1.30)	1.00 (0.70–1.42)	0.94 (0.66–1.34)	0.930	0.97 (0.85–1.10)
AOR (95% CI)	1.00 (ref)	0.86 (0.60–1.24)	0.96 (0.67–1.37)	0.92 (0.64–1.32)	0.873	0.96 (0.84–1.10)
SGA
Rate (%)	32 (5.5%)	46 (7.9%)	41 (7.0%)	47 (8.1%)	0.298
OR (95% CI)	1.00 (ref)	1.48 (0.93–2.35)	1.30 (0.81–2.10)	1.51 (0.95–2.41)	0.303	1.16 (1.02–1.33)
AOR (95% CI)	1.00 (ref)	1.54 (0.96–2.48)	1.39 (0.86–2.26)	1.62 (1.01–2.62)	0.208	1.17 (1.03–1.34)

Notes: Logistic regression models were adjusted for age, BMI, education background, smoking status, alcohol consumption status, conception method, parity, abortion history, thalassemia history and hemoglobin.

Abbreviations: SF, serum ferritin; LBW, low birth weight; LGA, large for gestational age; SGA, small for gestational age; OR odds ratio; AOR, adjusted odds ratio.

Figure 1 The association between SF and the risk of adverse pregnancy outcomes among pregnancy women with and without GDM. The model was adjusted for age, BMI, education background, smoking status, alcohol consumption status, conception method, parity, abortion history, thalassemia history and hemoglobin.