Fetal sex modifies effects of prenatal stress exposure and adverse birth outcomes

Figures & data

Table 1. Demographic and obstetric characteristics of the study population by exposure status.

	Total N = 4813	Exposed n = 1846	Unexposed n = 2967	Χ^2	p Value
	N (%)	N (%)	N (%)
Offspring sex				1.69	0.19
Males	2448 (50.9)	917 (49.7)	1531 (51.6)
Females	2365 (49.1)	929 (50.3)	1436 (48.4)
M/F ratio (95% Cl)	1.035 (0.978; 1.095)	0.987 (0.901; 1.081)	1.066 (0.992; 1.146)
Maternal age group				11.5	0.003
≤20	203 (4.2)	90 (4.9)	113 (3.8)
21–35	3878 (80.6)	1512 (81.9)	2366 (79.7)
>35	732 (15.2)	244 (13.2)	488 (16.4)
Marital status^a				0.47	0.92
Married	4377 (91.0)	1678 (90.9)	2699 (91.0)
Single	64 (1.3)	25 (1.4)	39 (1.3)
Divorced	363 (7.5)	139 (7.5)	224 (7.6)
Widow	8 (0.2)	4 (0.2)	4 (0.1)
Country of birth				4.66	0.032
Israel	3043 (63.8)	1132 (61.3)	1911 (64.4)
Other	1770 (36.8)	714 (38.7)	1056 (35.6)
Years of education^a				16.96	<0.001
<12 years	643 (14.5)	235 (13.6)	408 (15.0)
12	2493 (56.2)	921 (53.5)	1572 (57.9)
>12 years	1302 (29.3)	566 (32.9)	736 (27.1)
Mode of conception				1.35	0.22
Assisted reproductive technology	127 (2.6)	55 (3.0)	72 (2.4)
Spontaneous	4686 (97.4)	1791 (97.0)	2895 (97.6)
Parity^a				3.52	0.17
1	1463 (30.4)	582 (31.6)	881 (29.7)
2–3	2346 (48.8)	902 (48.9)	1444 (48.8)
>4	996 (20.7)	359 (19.5)	637 (21.5)
Gravidity^a				0.07	0.90
1	1229(25.5)	474 (25.7)	755 (25.5)
2–3	2097 (43.6)	800 (43.4)	1297 (43.7)
>4	1485 (30.9)	571 (30.9)	914 (30.8)
Background health problems^a,b	271 (5.6)	104 (5.6)	167 (5.6)	0.001	1.0
Bad obstetric history (among parity ≥ 2)^b	51 (1.1)	19 (1.0)	32 (1.1)	0.26	0.87
Gestational diabetes mellitus	341 (7.1)	143 (7.7)	198 (6.7)	1.99	0.16
Pregnancy-induced hypertension	294 (6.1)	113 (6.1)	181 (6.1)	0.001	0.99
Cesarean section	819 (17.0)	316 (17.1)	503 (17.0)	0.75	0.85

Bad obstetric history: history of intrauterine fetal death. Data is presented as numbers and percentages for categorical variables, and as ratio and confidence interval for M/F ratio.

^aMissing information: parity (n = 2), family status (n = 1), gravidity (n = 8), mode of delivery (n = 3), years of education: 605(10%). Background health problems: 1212 (20.1%).

^bBackground health problems, including: asthma, skin, connective tissue, heart, psychiatric or neurological conditions.

Table 2. Multivariable logistic models (GEE) for PTB and LBW in males and females.

	PTB				LBW
	Females		Males		Females		Males
Variables	Adjusted OR; 95% CI	p	Adjusted OR; 95% CI	p	Adjusted OR; 95% CI	p	Adjusted OR; 95% CI	p
Exposure status
Unexposed	1		1		1		1
Exposed	1.43; 1.04–1.96	0.029	1.30; 0.97–1.78	0.083	1.41; 1.02–1.95	0.039	1.27; 0.87–1.73	0.24
Maternal age at delivery
≤20	0.99; 0.48–2.03	0.98	1.56; 0.81–2.97	0.18	1.23; 0.64–2.37	0.53	2.02; 1.06–3.84	0.03
21–35	1		1		1		1
>35	0.73; 0.44–1.23	0.24	1.23; 0.80–1.89	0.34	0.86; 0.51–1.45	0.57	1.22; 0.73–2.04	0.46
Origin
Israel	1		1		1		1
Other	0.81; 0.58–1.12	0.19	0.80; 0.59–1.08	0.14	0.71; 0.50–0.98	0.044	0.91; 0.64–1.30	0.60
Parity
1	1		1		1		1
2–3	0.58; 0.41–0.84	0.004	1.05; 0.74–1.50	0.78	0.46; 0.31–0.66	<0.001	0.77; 0.52–1.13	0.18
≥4	0.89; 0.56–1.43	0.65	0.78; 0.48–1.28	0.30	0.82; 0.51–1.31	0.41	0.61; 0.353–1.07	0.08
Marital status
Married	1		1		1		1
Unmarried	1.31; 0.80–2.12	0.28	1.10; 0.66–1.81	0.72	1.42; 0.88–2.29	0.15	1.22; 0.71–2.09	0.48
Gestational diabetes mellitus	1.76; 1.03–3.00	0.041	1.67; 1.04–2.66	0.032	1.00; 0.52–1.92	0.99	0.76; 0.38–1.53	0.44
Pregnancy induced hypertension	2.02; 1.21–3.37	0.007	2.88; 1.86–4.46	<0.001	2.07; 1.23–3.46	0.006	2.12; 1.24–3.61	0.006

Table 3. Multivariable logistic model (GEE) for small HC in males and females.

	HC < 30				HC < 31
	Females		Males		Females		Males
Variables	Adjusted OR; 95% CI	p	Adjusted OR; 95% CI	p	Adjusted OR; 95% CI	p	Adjusted OR; 95% CI	p
Exposure status
Unexposed	1		1		1		1
Exposed	2.22; 0.96–5.10	0.058	0.44; 1.54–1.24	0.12	1.78; 1.11–2.88	0.018	0.80; 0.42–1.51	0.49
Origin
Israel	1		1		1		1
Other	1.51; 0.63–3.60	0.35	0.41; 0.16–1.04	0.062	0.82; 0.50–1.32	0.41	0.62; 0.34–1.15	0.13
Gestation week	0.43; 0.37–0.51	<0.001	0.40; 0.34–0.48	<0.001	0.50; 0.45–0.56	<0.001	0.45; 0.39–0.51	<0.001
Gestational diabetes mellitus*	0.24; 0.04–1.47	0.12	0.50; 0.08–3.04	0.46	0.71; 0.29–1.72	0.45	0.95; 0.34–2.61	0.92

*Results remained similar after removing GDM from the models.

Figure 1. Secondary sex ratio by gestational age categories, in the exposed and unexposed groups.

Figure 2. Secondary sex ratio by birthweight categories, in the exposed and unexposed groups.

Figure 3. Secondary sex ratio by small for gestational age status, in the exposed and unexposed groups.

Figure 4. Secondary sex ratio by head circumference, in the exposed and unexposed groups.