Growth in the first two years in children born to mothers infected with COVID-19 during pregnancy: a cohort study

Abstract

Introduction

Because the impact of COVID-19 on the growth of infants whose mothers were infected with this virus during pregnancy is unclear, this study investigated the effect of mothers’ infection with this virus during pregnancy on their infant’s growth during the first two years of life.

Method

In this prospective cohort study, the available information from 697 mothers referring to Iran’s health care centers for pregnancy and breastfeeding care was used to compare the growth of 367 children born to mothers infected with COVID-19 during pregnancy with that of 330 children born to mothers who were not infected and not exposed to COVID-19 during pregnancy. Their growth was evaluated for two years.

Results

Concerning the weight, height, and head circumference 6 months, 12 months, and 24 months after birth, although the values obtained in the exposed group were slightly higher than the non-exposed group, no statistically significant difference was observed (P > 0.05). Comparing the exposed group’s growth indices (weight, height, and head circumference) based on whether the mother was infected with COVID-19 during the first, second, or third trimester showed no significant difference (P > 0.05). The birth height of the babies whose mothers infected with COVID-19 in the first and second trimesters of pregnancy was slightly lower than those whose mothers were infected in the third trimester (P = 0.019). Children in the exposed group weighed 76.61 g more than those in the non-exposed group (P = 0.018).

Conclusion

More long-term studies in different populations about growth of children are needed to generalized the findings.

Clinical trial number

Not applicable (A cohort study).

Introduction

COVID-19 is the disease classified as a pandemic in 2019. It is highly contagious [1] and manifests with symptoms such as fever, shortness of breath, cough, fatigue, and muscle pain. The virus is constantly mutating and circulating in the world [2]. During the deadly epidemic and pandemic of COVID-19, two of the groups at risk were pregnant and breastfeeding women. Mothers and children are among the groups at very high risk of contracting the virus [3]. Little information is available on the effects of this virus on pregnancy outcomes and its effect on the fetus [4]. Although vertical transmission from infected pregnant mothers to fetuses has rarely been observed [3, 5], some studies have reported outcomes such as spontaneous abortion, premature birth, intrauterine growth restriction, endometrial intubation, hospitalization in the intensive care unit, renal failure, and coagulation disorders during pregnancy [6, 7].

Although the findings about the effects of infection during pregnancy on the fetus are scarce, one study showed that some babies born to mothers infected with COVID-19 suffered from acute respiratory syndrome and pneumonia [6]. The Apgar score was 7 in the first minute and 8 in the fifth minute, and the babies had no abnormalities. The breast milk samples of these mothers were free of the virus [8]. According to a study based on gestational age, pregnant women with a positive COVID-19 PCR test had significantly higher fevers between 14 and 36 weeks of gestation than those at 37 weeks or later and preeclampsia and gestational diabetes decreased with their gestational age. But at different gestational ages, there was no difference in the incidents of small for gestational age as well as Apgar scores (lower than 7) in the fifth minute. A significant difference was observed with the increase in the admission rate in the neonatal intensive care unit (NICU) department at the gestational ages of 28 to 36 weeks compared to other gestational ages. In addition, this study showed that the gestational age at the time of contracting COVID-19 was not related to premature delivery [9].

According to the results of a study, infection with COVID-19 does not increase the incidence of developmental disorders in 6-month-old infants. Furthermore, it does not increase low birth weight and premature delivery. Due to the limitations of the study, it is suggested to conduct a study with a larger number of pregnant mothers with a severe form of the disease, especially in the first trimester of pregnancy, and to follow up with the babies at an older age [10]. As infected mothers may have had negative test results, such a comparison may not be reliable.

Because the impact of COVID-19 on the growth of infants whose mothers were infected with this virus during pregnancy is unclear, and there are few studies in this field, in this study, which was conducted as a prospective cohort, the effect of mothers’ infection with this virus during pregnancy on their infant’s growth during the first two years of life was investigated.

Method

In this prospective cohort study, the available information from people referring to Iran’s health care centers for pregnancy and breastfeeding care was used to compare the growth of children born to mothers infected with COVID-19 during pregnancy with that of children born to mothers who were not infected and not exposed to COVID-19 during pregnancy. Infants born to mothers who were not infected or exposed to COVID-19 during pregnancy (group N, the non-exposed group) and with the closest delivery date to December 2019 (before the start of COVID-19 based on the epidemiological rotation of the disease) were selected to minimize the difference in birth dates between the two groups. Their growth was evaluated for two years. Mothers who gave birth before the epidemiological onset of the disease were considered as a control group (non-exposed) to ensure that there were no PCR false negatives for COVID-19.

Infants born to mothers who were exposed to and infected with COVID-19 during pregnancy (group E, the exposed group), with a birth date between February 20, 2020, and October 20, 2020, were examined for two years. The criterion for these mothers was having at least one positive PCR test during pregnancy.

The cluster sampling method was used as follows: Iran was divided into five parts: north, south, east, west, and center, and one province was selected from each part. The number of samples assigned to each cluster was based on the geographical size and population of that region. The data were collected from each provincial capital’s Vice-Chancellor of Health of the University of Medical Sciences.

The inclusion criteria for group E included the mothers’ positive PCR test during pregnancy and the mothers’ consent to participate in the study. Also, the baby had to be free of diseases or abnormalities that affect growth. The inclusion criteria for group N included mothers’ consent to participate in the study with delivery dates before and closest to December 1, 2019. Also, the baby had to be free of diseases or abnormalities that affect growth.

The exclusion criteria were non-participation of the mother, change of the mother’s contact number, and lack of access to the mother or other relatives.

Factors affecting the infant’s growth, including parents’ socio-economic status and race, the baby’s gender, and the mother’s diseases during pregnancy, were included in the demographic information for homogenization.

The control group of infants from each province was selected from the same province. In this study, the growth of children during the first two years was investigated. The sample size was 300 people for the exposed group and 300 people for the unexposed group.

After receiving the ethical code, the information resources of the Vice-Chancellor of Health in the relevant universities in each province were used to collect data on the participants of group E, i.e., pregnant mothers who gave birth between February 20, 2020, and October 20, 2020, and who were confirmed to be infected with COVID-19 based on the PCR test. In addition, based on the sample size, group N mothers with the closest delivery date before December 2019 were also selected.

The participants’ contact numbers and health file numbers were acquired, and they were contacted after checking the entry criteria. After receiving an explanation of the study plan and providing a written consent form, they were included. Information related to child development was collected in each province by calling the mother and using the SIB system. In order to avoid false negative COVID-19 PCR tests, mothers who gave birth before the epidemiological onset of the disease were considered.

The outcome of the study was the growth of children within two years after birth, including weight, height, and head circumference, which were recorded at the ages of 2 months, 4 months, 6 months, 8 months, 10 months, 12 months, 14 months, 16 months, 18 months, 20 months, 22 months, and 24 months.

Statistical analysis

Descriptive statistics, such as frequencies and percentages, were provided for variables in both the exposed and unexposed groups. The chi-square test was conducted to compare covariates between the two groups. Independent t-test was used to compare growth indicators (weight, height, and head circumference) in different months in exposed and unexposed groups. In addition, the ANOVA test was used to compare growth indicators (weight, height, and head circumference) based on maternal coronavirus infection in the first, second, and third trimesters of pregnancy only in the exposed group. Bivariable and multivariable mixed effects linear regression models were developed to explore the growth trend depending on weight, height, and head situation. The final model was chosen using a backward elimination approach. The results contained regression coefficients as well as P-values. These data were processed with Stata 14.1 (College Station, Texas). P-values less than 0.05 were considered statistically significant.

Results

This study included 697 participants, of whom 367 were exposed, and 330 were not. Most mothers who participated in this study were between the ages of 21 and 40 years, accounting for 89.9% and 92% of the participants in the exposed and unexposed groups, respectively. Most mothers had a BMI in the normal range of 18.5–24.9, accounting for 39.5% and 43% of the participants in the exposed and non-exposed groups, respectively, and the difference was statistically significant (P = 0.014).

According to the findings, most of the study’s participants performed screening tests during pregnancy, including 84.5% in the exposed group and 85.2% in the non-exposed group. The delivery method of more than half of the mothers participating in this study was cesarean, 53.5% and 51.1% in the exposed and non-exposed groups, respectively (Table 1).

Table 1.

Characteristics of mothers as frequency and percentage: n (%)

Covariates	Levels of covariates	Exposed group	Unexposed group	P-value
Age (mother)	≤ 20	21 (6.0)	10 (3.1)	0.262
	21–30	166 (47.6)	152 (46.8)
	31–40	149 (42.7)	147 (45.2)
	Above 40	13 (3.7)	16 (4.9)
Age (father)	≤ 20	1 (0.3)	-	0.620
	21–30	88 (26.4)	91 (28.5)
	31–40	209 (62.8)	190 (59.6)
	Above 40	35 (10.5)	38 (11.9)
Number of children	1	122 (35.2)	111 (34.4)	0.498
	2	130 (37.5)	134 (41.5)
	≥ 3	95 (27.4)	78 (24.1)
BMI	< 18.5	8 (3.8)	21 (11.3)	0.014
	18.5–24.9	83 (39.5)	80 (43.0)
	25–29.9	78 (37.1)	60 (32.3)
	≥ 30	41 (19.5)	25 (13.4)
History of mother’s disease pre-pregnancy	No	290 (79.0)	272 (82.4)	0.264
	Yes	77 (21.0)	58 (17.6)
History of mother’s disease during pregnancy	No	279 (76.0)	241 (73.0)	0.353
	Yes	88 (24.0)	89 (27.0)
Screening tests	No	57 (15.5)	49 (14.8)	0.729
	Yes	310 (84.5)	281 (85.2)
Need for blood transfusion after delivery	No	365 (99.5)	330 (100.0)	0.180
	Yes	2 (0.5)	-
Hospitalization due to infection or embolism	No	359 (97.8)	319 (96.7)	0.347
	Yes	8 (2.2)	11 (3.3)
Type of delivery	Natural	164 (46.5)	159 (48.9)	0.521
	C-section	189 (53.5)	166 (51.1)

Note: Due to missing data, the number in the table may be lower than the total number in each group

• The chi-square test

In this study, there were more male than female infants, with 51.2% and 52.5% in the exposed and non-exposed groups, respectively. Most of the babies’ birth weights were between 2501 and 3500 g, accounting for 72.7% and 77.2% of the exposure and non-exposure groups, respectively.

Furthermore, the birth height of most newborns was between 41 and 50 cm, with 70.6% in the exposure group and 62.5% in the non-exposure group, and the head circumference of most of the babies was between 25 and 35 cm, with 80.5% and 81% in the exposed and non-exposed groups, respectively. The babies were more frequently breastfed, with 61.9% in the exposed group and 70.9% in the non-exposed group, which was significantly different (P = 0.005) (Table 2).

Table 2.

Characteristics of infants as frequency and percentage: n (%)

Covariates	Levels of covariates	Exposed	Non-exposed	P-value
Gender	Boy	174 (51.2)	168 (52.5)	0.734
	Girl	166 (48.8)	152 (47.5)
Apgar	≤ 7	1 (0.3)	2 (1.6)	0.145
	8	3 (0.8)	7 (5.9)
	9	94 (25.6)	99 (83.9)
	10	20 (5.4)	10 (8.5)
Infant’s weight	1500–2500	32 (9.7)	22 (7.3)	0.320
	2501–3500	240 (72.7)	233 (77.2)
	3501–4500	56 (17.0)	47 (15.6)
	Ȗ 4500	2 (0.6)	-
History of hospitalization in the neonatal ward after birth	No	317 (86.4)	229 (69.4)	< 0.001
	Yes	50 (13.6)	100 (30.6)
Jaundiced	No	199 (54.2)	141 (42.7)	0.003
	Yes	168 (45.8)	188 (57.3)
Need for surgery at birth	No	362 (98.6)	257 (77.9)	< 0.001
	Yes	5 (1.4)	73 (22.1)
Congenital disease	No	364 (99.2)	263 (79.7)	< 0.001
	Yes	3 (0.8)	67 (20.3)
Working mother	No	307 (83.7)	279 (84.5)	0.678
	Yes	60 (16.3)	51 (15.5)
Caretaker	Mother	290 (86.8)	290 (90.1)	0.007
	Grandmother	19 (5.7)	25 (7.8)
	Nurse	10 (3.0)	2 (0.6)
	Other	15 (4.5)	5 (1.5)
Place of childcare	Home	292 (86.6)	313 (97.5)	< 0.001
	Kindergarten or other	45 (13.1)	8 (2.5)
Infant’s nutrition	Baby formula	50 (14.3)	22 (6.9)	0.005
	Breastfeeding	216 (61.9)	227 (70.9)
	Both	83 (23.8)	71 (22.2)

Note: Due to missing data, the number in the table may be lower than the total number in each group

• The chi-square test

Concerning the weight, height, and head circumference 6 months, 12 months, and 24 months after birth, although the values obtained in the exposed group were slightly higher than the non-exposed group, no statistically significant difference was observed (P > 0.05) (Table 3).

Table 3.

Comparison of growth indicators (weight, height, and head circumference) in different months in exposed and non-exposed groups

Covariates	Exposed	Unexposed	P-value
Birth weight	3132.64 ± 503.46	3117.02 ± 455.98	0.675
Weight at 6 months	7518.94 ± 973.39	7487.09 ± 893.52	0.663
Weight at 12 months	9330.01 ± 1194.31	9291.09 ± 1181.63	0.675
Weight at 24 months	11820.56 ± 1724.46	11656.51 ± 3038.53	0.459
Birth height	49.54 ± 2.68	49.78 ± 2.70	0.242
Height at 6 months	67.39 ± 2.88	66.97 ± 2.51	0.051
Height at 12 months	75.55 ± 3.22	75.58 ± 2.69	0.910
Height at 24 months	86.77 ± 5.76	86.73 ± 3.65	0.924
Head circumference at birth	34.74 ± 4.57	34.66 ± 3.31	0.805
Head circumference at 6 months	42.84 ± 2.01	42.71 ± 1.34	0.333
Head circumference at 12 months	45.70 ± 2.29	45.66 ± 1.33	0.772
Head circumference at 24 months	48.25 ± 4.05	48.08 ± 1.46	0.639

• Independent t-test analysis

We also compared the exposed group’s growth indices (weight, height, and head circumference) based on whether the mother was infected with COVID-19 during the first, second, or third trimester. No significant difference was seen (P > 0.05). The birth height of the babies whose mothers who were infected with COVID-19 in the first and second trimesters of pregnancy was slightly lower than those whose mothers were infected in the third trimester (P = 0.019) (Table 4).

Table 4.

Comparison of growth indicators (weight, height, and head circumference) based on the mother’s infection with coronavirus in the first, second, and third trimesters of pregnancy (Exposed group)

Infant	Mother’s pregnancy	Mean	Std. Deviation	P-value
Birth weight	First three months	3184.19	489.92	0.707
	Second three months	3126.42	491.51
	Third three months	3161.19	496.19
Weight at 6 months	First three months	7632.57	976.92	0.541
	Second three months	7549.13	993.63
	Third three months	7476.35	939.31
Weight at 12 months	First three months	9345.21	1182.96	0.956
	Second three months	9385.87	1245.10
	Third three months	9345.28	1127.18
Weight at 24 months	First three months	11650.00	1460.40	0.455
	Second three months	11993.83	1678.28
	Third three months	11777.47	1721.80
Birth height	First three months	49.73	3.04	0.019
	Second three months	49.06	2.75
	Third three months	50.00	2.35
Height at 6 months	First three months	67.66	2.59	0.123
	Second three months	67.02	3.33
	Third three months	67.71	2.54
Height at 12 months	First three months	75.68	2.61	0.532
	Second three months	75.39	3.88
	Third three months	75.84	2.76
Height at 24 months	First three months	86.99	3.42	0.821
	Second three months	86.39	7.47
	Third three months	86.79	4.97
Head circumference at birth	First three months	34.68	2.23	0.230
	Second three months	35.33	7.27
	Third three months	34.31	1.46
Head circumference at 6 months	First three months	42.82	1.38	0.073
	Second three months	43.21	2.78
	Third three months	42.64	1.27
Head circumference at 12 months	First three months	45.57	1.43	0.052
	Second three months	46.15	3.31
	Third three months	45.46	1.29
Head circumference at 24 months	First three months	47.86	1.09	0.309
	Second three months	49.05	6.40
	Third three months	47.91	1.28

• the ANOVA test

Investigating growth

Examining the growth trend of children based on weight revealed that children’s weight increased by an average of 997.46 g with increasing age per two months (P < 0.001). Weight increase differed significantly between the exposed and non-exposed groups; children in the exposed group weighed 76.61 g more than those in the non-exposed group (P = 0.018). Boys weighed 479.45 g more than girls as they grew older in this period, which was statistically significant (P < 0.001). Children cared for in places such as kindergartens gained 267.50 g more weight as they age increased in this period than children cared for at home (P < 0.001) (Table 5).

Table 5.

The effect of covariates on infant’s weight trends using mixed-effects linear regression

Covariates	Levels	Crude		Adjusted
		Coefficient	P-value	Coefficient	P-value
Time		994.12	< 0.001	997.46	< 0.001
Group	Non-exposed	Ref		Ref
	Exposed	35.25	0.264	74.61	0.018
Age (mother)		-1.56	0.603
Age (father)		4.50	0.158
Number of children		-9.71	0.585
BMI (mother)		26.47	< 0.001
History of mother’s disease pre-pregnancy	No	Ref
	Yes	75.24	0.107
History of mother’s disease during pregnancy	No	Ref
	Yes	67.61	0.110
Screening tests	No	Ref
	Yes	61.56	0.245
Need for blood transfusion after delivery	No	Ref
	Yes	561.54	0.081
Hospitalization due to infection or embolism	No	Ref
	Yes	227.97	0.055
Type of delivery	Natural	Ref
	C-section	18.64	0.616
Gender	Girl	Ref		Ref
	Boy	587.50	< 0.001	479.45	< 0.001
Apgar		18.48	0.761
Birth weight		0.90	< 0.001	0.78	< 0.001
Birth height		61.02	< 0.001
Head circumference at birth		77.42	< 0.001
History of hospitalization in the neonatal ward after birth	No	Ref
	Yes	-21.58	0.630
Jaundiced	No	Ref
	Yes	4.55	0.904
Need for surgery at birth	No	Ref
	Yes	-81.68	0.166
Congenital disease	No	Ref
	Yes	-10.65	0.863
Working mother	No	Ref
	Yes	191.86	< 0.001
Caretaker	Mother	Ref
	Grandmother	64.51	0.401
	Nurse	257.37	0.130
	Other	-20.84	0.850
Place of childcare	Home	Ref		Ref
	Kindergarten or other	465.56	< 0.001	267.50	< 0.001
Infant’s nutrition	Breastfeeding	Ref
	Baby formula	-120.86	0.050
	Both	-163.39	< 0.001

• mixed effects linear regression

The examination of growth based on height found that as the children’ age increased in this period, their height increased by 4.36 cm (P < 0.001). The height of boys was 0.96 cm higher than girls (P < 0.001), and the height of children who were fed formula was 0.65 cm higher than those who were breastfed (P = 0.001) (Table 6).

Table 6.

The effect of covariates on infant’s height trends using mixed-effects linear regression

Covariates	Levels	Crude		Adjusted
		Coefficient	P-value	Coefficient	P-value
Time		4.37	< 0.001	4.36	< 0.001
Group	Non-exposed	Ref		Ref
	Exposed	0.08	0.347	0.15	0.131
Age (mother)		-0.01	0.038	-0.03	< 0.001
Age (father)		-0.008	0.393
Number of children		0.10	0.060	0.19	0.002
BMI (mother)		0.05	< 0.001
History of mother’s disease pre-pregnancy	No	Ref
	Yes	0.18	0.202
History of mother’s disease during pregnancy	No	Ref
	Yes	0.05	0.697
Screening tests	No	Ref
	Yes	0.20	0.211
The need for blood administration after delivery	No	Ref
	Yes	-0.41	0.677
Hospitalization due to infection or embolism	No	Ref
	Yes	0.83	0.023
Type of delivery	Natural	Ref
	C-section	0.01	0.917
Gender	Girl	Ref		Ref
	Boy	1.18	< 0.001	0.96	< 0.001
Apgar		-0.18	0.400
Birth weight		0.002	< 0.001	0.001	< 0.001
Birth height		0.24	< 0.001	0.16	< 0.001
Head circumference at birth		0.24	< 0.001	0.15	< 0.001
History of hospitalization in the neonatal ward after birth	No	Ref
	Yes	-0.60	< 0.001
Jaundiced	No	Ref
	Yes	0.12	0.277
Need for surgery at birth	No	Ref
	Yes	0.02	0.903
Congenital disease	No	Ref
	Yes	-0.17	0.362
Working mother	No	Ref
	Yes	0.27	0.061
Caretaker	Mother	Ref
	Grandmother	-0.18	0.416
	Nurse	0.72	0.125
	Other	0.71	0.031
Place of childcare	Home	Ref
	Kindergarten or other	0.82	< 0.001
Infant’s nutrition	Breastfeeding	Ref		Ref
	Baby formula	0.20	0.260	0.65	0.001
	Both	-0.15	0.249	0.20	0.156

• mixed effects linear regression

Examining the growth trend based on head circumference revealed that as children’ age increased in this period, their head circumference grew by 1.63 cm (P < 0.001), and kids whose mothers had screening tests during pregnancy had a head circumference 0.49 cm larger than those who did not (P < 0.001). The head circumference of boys was 0.95 cm greater than that of girls (P < 0.001) (Table 7).

Table 7.

The effect of covariates on infant’s head circumference trends using mixed-effects linear regression

Covariates	Levels	Crude		Adjusted
		Coefficient	P-value	Coefficient	P-value
Time		1.63	< 0.001	1.63	< 0.001
Group	Non-exposed	Ref		Ref
	Exposed	0.13	0.047	0.11	0.119
Age (mother)		0.003	0.603
Age (father)		0.007	0.287
Number of children		-0.06	0.100
BMI (mother)		0.02	0.056
History of mother’s disease pre-pregnancy	No	Ref
	Yes	0.09	0.376
History of mother’s disease during pregnancy	No	Ref
	Yes	0.06	0.479
Screening tests	No	Ref		Ref
	Yes	0.43	< 0.001	0.49	< 0.001
The need for blood transfusion after delivery	No	Ref
	Yes	0.65	0.379
Hospitalization due to infection or embolism	No	Ref
	Yes	-0.24	0.378
Type of delivery	Natural	Ref
	C-section	-0.01	0.825
Gender	Girl	Ref		Ref
	Boy	1.13	< 0.001	0.95	< 0.001
Apgar		0.50	0.017
Birth weight		0.001	< 0.001	0.004	< 0.001
Birth height		0.06	< 0.001	0.05	< 0.001
Head circumference at birth		0.19	< 0.001	0.13	< 0.001
History of hospitalization in the neonatal ward after birth	No	Ref
	Yes	-0.02	0.818
Jaundiced	No	Ref
	Yes	-0.17	0.036
Need for surgery at birth	No	Ref
	Yes	0.32	0.014
Congenital disease	No	Ref
	Yes	0.45	0.001
Working mother	No	Ref
	Yes	0.54	< 0.001	0.27	0.021
Caretaker	Mother	Ref
	Grandmother	1.03	< 0.001
	Nurse	0.51	0.141
	Other	-0.007	0.976
Place of childcare	Home	Ref
	Kindergarten or other	-0.002	0.989
Infant’s nutrition	Baby formula	Ref
	Breastfeeding	-0.64	< 0.001
	Both	-0.60	0.534

• mixed effects linear regression

Discussion

This cohort study was conducted to compare the growth of children of mothers exposed to COVID-19 during pregnancy with children of mothers who were not exposed to the disease. This study showed no statistically significant difference between the growth parameters, including weight, height, and head circumference at birth and the ages of 6 months, 12 months, and 24 months in children of mothers exposed to COVID-19 during pregnancy and those not exposed, which means that the mothers’ infection with COVID-19 during pregnancy did not affect growth in the first two years of their children’s lives. Meanwhile, Mollie’s study in 2023 showed that infants exposed to COVID-19 in the womb had lower birth weight and more rapid weight gain in the first year of their life compared to unexposed mothers [11]. Contrary to Mollie’s study, the results of the present study showed that birth weight was not different between the two groups. Perhaps it can be concluded that mothers exposed to COVID-19 have tried to take serious care during the rest of their pregnancy due to fear and concern about the negative impact of the disease on the child’s growth and development. As observed during the COVID-19 pandemic, new mothers felt anxious and uncomfortable. They were mainly concerned about the physical health of their children and the state of nutrition and care of their children [12]. In this regard, it has been shown that pregnant women admitted to midwifery departments used self-care methods such as wearing masks, washing their hands regularly, and reminding the personnel to wash their hands before providing care to reduce the risks of COVID-19 [13]. A study conducted in South Carolina showed that the rate of preterm labor increased during the COVID-19 pandemic, but the low birth weight was different based on race, and the Spanish race had lower birth weight before the pandemic [14]. This may also be one of the justifications for the lack of low birth weight in the exposed mothers in the current study.

The findings indicated that the mother’s infection during pregnancy did not adversely affect the head growth of the infant. Contrary to these findings, previous studies showed that other infectious diseases of the mother affected the child’s head circumference. A study in Brazil showed that the mother’s malaria infection during pregnancy caused microcephaly in the infant [15]. Of course, the type of the pathogenic agent, the onset mechanism of the disease, and the ways of its transmission should be considered when discussing complications and mortality, which can justify the contrast between the findings of the studies. In addition, previous studies have shown that there is a positive relationship between the mother’s education and occupation and the birth weight, height, and head circumference of the infant in the first 18 months [16], which indicates the impact of various factors on this measurement criterion and requires broader studies examining various influential factors.

Height growth at birth and other ages in children of exposed mothers was not different from that of unexposed mothers. Although 60 to 80% of height growth depends on genetics, environmental factors, especially factors such as nutrition and fetal diseases, influence it by 20–40%. Following this notion, Karimi’s study showed that fasting during pregnancy, which causes long-term hunger in the mother, decreased the height of male children between 3 and 4 years [17]. As stated earlier, the change in the behavior of pregnant mothers during the COVID-19 pandemic can be a factor in the lack of effect of the disease on growth factors. According to a survey, it was found that the COVID-19 pandemic has caused a positive change in the health behaviors of pregnant women (correct dietary habits with a particular focus on the type of food consumed, preventive behaviors in terms of following health recommendations and obtaining information about health and diseases, daily habits regarding sleep, rest, and physical activity as well as positive mental attitudes, i.e., avoiding excitement, stress, and depressing situations) [18], which can be a reason for the lack of difference in height growth compared to unexposed mothers.

Children suffering from diseases can be negatively affected in terms of their weight and height growth. The results of the current study showed that during the two years of follow-up, despite the COVID-19 pandemic, children’s growth did not differ from the pre-COVID-19 period. One of the reasons for this lack of difference has been the quarantine during the pandemic, which caused people to have less contact with each other, observe social distancing, wash hands regularly, etc. Various studies have shown that during the COVID-19 quarantine, the prevalence of other diseases has decreased compared to previous years. In this regard, a survey showed that invasive infections with respiratory bacterial pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Bordetella pertussis, Chlamydia pneumoniae, and Mycoplasma pneumoniae, have decreased significantly in several countries of the world [19]. According to another review, a set of measures introduced by COVID-19, including an emphasis on personal hygiene and social distancing, had unexpectedly large positive effects on otitis media, suppressing its onset and exacerbation [20].

In this study, a comparison was also made between the children of exposed mothers based on the gestational age, and it was observed that the development status of the children did not differ from each other based on the trimester of pregnancy the mother was infected in. Although there was a statistically significant relationship between the height of children at birth and the mother’s disease in the first and second trimester and the third trimester, this relationship was only one centimeter and had no clinical value. As Yi stated, the timing of the mother’s COVID-19 infection during pregnancy does not make a difference in pregnancy outcomes [21]. A comprehensive study evaluated children at 3-month intervals for weight, height, and head circumference growth. All enrolled children had normal growth regardless of time or severity of maternal infection [22]. In this regard, a retrospective cohort study concluded that asymptomatic or mildly symptomatic women in the first trimester of pregnancy did not report significant side effects compared to SARS-CoV-2-negative women [23]. The results of another study also showed that there was no significant relationship between birth weight and the time of COVID-19 infection during pregnancy [24].

Limitations

The babies of mothers who were exposed to COVID 19 during pregnancy had a lower rate of being hospitalized in the neonatology ward after birth (13.6% vs. 30%, p < 0.001) and jaundiced less (45.8% vs. 57.3%, p = 0.003), less need for surgery (1.4% vs. 22.1%, p < 0.001), had lower rates of congenital disease (0.8% vs. 20.3%, p < 0.001), etc. This may reflect differences between the COVID-19 period and the pre-COVID-19 period in terms of hygiene rules, quarantine practices, etc. Our findings should be evaluated with caution due to the significant comorbidity differences between the study and control groups. The other limitation is that the control group selected from pre-COVID period to be sure that false- negative mothers are not included in this group but we may miss the time-related distorting factors such as economic and social status of the country.

As the evaluation of the effect of the severity of maternal COVID-19 (mild, moderate, severe, or those requiring hospitalization vs. those not requiring hospitalization) on growth parameters was not feasible, it is suggested as a second study proposal.

Conclusion

No significant difference was seen between the weight, height and head circumference of children whose mothers infected with COVID-19 during pregnancy and non-infected ones. More long-term studies in different populations about growth of children are needed to generalized the findings.

Author contributions

H.N.B. sponsorship and research design, A.A. research design, last draft, study protocol, M. P. research management, F. K. and E.K. and F.S.T. and F.J. and F.H. data collection, S.D. and K.A. and M.Gh. first draft, P.J.A. and H. SH data analysis.

Funding

National Institute of Medical Research Islamic Republic of Iran (ID: 993678).

Data availability

“All data supporting the results of this study are not publicly available due to participant confidentiality but are available from the corresponding author upon reasonable request.“,

Declarations

Ethics approval and consent to participate

This is to certify that this research with Reg. No. 99000029 was approved by ethical committee of Kerman University of Medical Sciences. The Ethic Approval Code is IR.KMU.REC.1399.210. All of the women in the exposed group filled the informed consent form to participate in the study with their child. In addition, the women in the non-exposed group were called to get their permission in the study. And it was easy for participants to withdraw from the study whenever they were willing. At the request of the ethics committee, the study was conducted in accordance with the Declaration of Helsinki and Ethics Publication on Committee (COPE). Special codes were used for each of the participants to ensure the confidentiality of information.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.