The effect of Coronavirus disease pandemic on maternal and neonatal health: A cohort study from Isfahan, Iran

Abstract Background The Coronavirus disease-2019 (COVID-19) pandemic may profoundly impact on maternal and neonatal health worldwide. However, a few studies have investigated this topic. Objective This study aimed to investigate the impact of the COVID-19 pandemic on maternal and neonatal health. Materials and Methods This retrospective cohort study analyzed collected data from March to May 2020, and the same period in 2019, involving 5711 pregnant women referring to comprehensive healthcare centers in Isfahan province health facilities, Iran. Pregnant women and neonates were followed-up until 40 days after the delivery. Demographic characteristics, pre-pregnancy, antenatal care, and post-pregnancy variables were collected. Results A total of 5711 pregnant women were studied, of whom 3477 (61%) were referred in 2019 (before the COVID-19 pandemic as nonexposed) and 2234 (39%) during the COVID-19 pandemic (as exposed group) in 2020. For those living in cities with a population of > 20,000, the number of antenatal care were lower about 2% compared to nonexposed group (p = 0.01). The number of mothers with a history of the underlying disease who referred to a comprehensive healthcare center during the COVID-19 pandemic (47%) was lower about 6% compared to nonexposed group (41%) (p < 0.001). During the COVID-19 pandemic, the prevalence of hypertension and gestational diabetes mellitus was 5% (n = 109) and 20% (n = 445), which were higher about 2% and 4%, respectively, compared to nonexposed group. The COVID-19 pandemic had no other significant effect on mothers' and neonates' other characteristics than nonexposed group. Conclusion The COVID-19 pandemic imposes no significant effect on mothers' and neonates' health compared to nonexposed group.


Introduction
Noteworthy, the impact of the COVID-19 pandemic on maternal and neonatal health is not limited to the morbidity and mortality caused directly by the disease itself (7).
In this line, this study aimed to evaluate the effect of the COVID-19 pandemic on maternal and neonatal health among pregnant women referring to comprehensive healthcare centers in Isfahan province of Iran.

Study design
Following a retrospective cohort design, data of all pregnant women whose last menstrual period dates were from March to May, 2019 (before the pandemic as nonexposed group) and referred to an urban or rural comprehensive healthcare center in Isfahan province, Iran (n = 3477) and all those who referred to these centers during this period in 2020 (during the pandemic as exposed group) (n = 2234), were surveyed. Required data were extracted from the electronic health records of participants.

Study variables
Data on the following variables were collected: • Demographic characteristics, including age and place of residence (i.e., cities > 20,000 population, cities < 20,000 population, villages, and marginalized areas); • Pre-pregnancy variables, including weight, history of abortion, number of previous pregnancies, and history of underlying disease; • Antenatal care, including the number of antenatal consultations, risky symptoms during pregnancy (e.g., hypertension, gestational diabetes, dyspnea, edema, and hemorrhage); and • Post-pregnancy variables include height, weight, head circumference, type of delivery, and neonatal status (alive or stillbirth). Data on study variables were extracted from the electronic health records of participants.
The physician or midwife of the center was interviewed in cases where a variable was missed.
Those participants with > 20% missing data were excluded from the study.

Ethical considerations
The research purpose and methodology

Statistical analysis
Categorical variables were described as frequencies (%) and continuous as Mean ± SD.
After assessing normality distribution-with the Shapiro-Wilk test-the Mann-Whitney test was used to compare the mean of continuous characteristics between pre-pandemic (2019) and intra-pandemic
Although the number of cases with a history of abortion (25%; n = 548) was significantly lower during the COVID-19 pandemic than nonexposed; however, the percentage of people with a previous history of preeclampsia was higher in this period (4.6%; n = 102).
Generally, the number of mothers with a history of the underlying disease who referred to a comprehensive healthcare center during the COVID-19 pandemic (47%; n = 1052) was lower about 6% in comparison to nonexposed group (41%; n = 1414) (p < 0.001). Also, diabetes was more prevalent among mothers who referred to a comprehensive healthcare center during the COVID-19 pandemic about 1% (p < 0.001, Table I). As shown in table II, the prevalence of abortion (2%; n = 48) and abdominal or flank pain (3%; n = 58) higher by 2x in exposed group compared to nonexposed group, which was statistically significant. Also, in exposed group, 16% (n = 362) of pregnant women had vaginal delivery, which higher about 4% in comparison to nonexposed group (p < 0.001).
In exposed group, the prevalence of hypertension and gestational diabetes mellitus was 5% (n = 109) and 20% (n = 445), which were higher about 2% and 4%, respectively, compared to nonexposed group. NMR was also lower about 5% during the COVID-19 pandemic compared to nonexposed group, which was statistically significant. As shown in table II, the COVID-19 pandemic imposed no significant effect on mothers' and neonates' other characteristics compared to nonexposed group. Table I. Demographic and baseline maternal characteristics of pregnant women complications in the exposed group and nonexposed group

Characteristics
Total (n = 5711) Nonexposed group (n = 3477)   hemorrhage, neonate death, low-birth weight (< 2500 gr), and preterm delivery rate (7). A retrospective cohort study that intended to investigate the effect of the first COVID-19 peak on prenatal morbidity and mortality found a higher rate of stillbirth during the COVID-19 pandemic than nonexposed group. Gestational age, preterm labor rate, pregnancy complications, and complications of delivery and its type were similar in both groups (10). The other study in line with the present study's findings showed no association between preterm labor and stillbirth and birth during the COVID-19 pandemic (11).

Discussion
In a study conducted in Nigeria, the authors mentioned a 22% increase in stillbirth and 23% in neonatal mortality rate during the COVID-19 pandemic compared to nonexposed group (12).
The difference between the findings of the study conducted in Nigeria and the present study can be attributed to differences in participants' social, cultural, and economic characteristics and the retrospective design of the Nigeria study.
In a study conducted in London, reported lower rates of pregnancy hypertension and higher rates of stillbirth among pregnant women during the COVID-19 pandemic compared to nonexposed group, which is against the present study's findings. However, there is no difference between these 2 studies concerning the frequency of preterm labor (13). Another study reported no difference in the rate of preterm delivery, stillbirth, and other perinatal complications (14). In another study conducted during the COVID-19 pandemic, the authors mentioned declined rate of C-sections with the observance of new protocols; however, this decline was not associated with increased mortality and morbidity. The current study's findings contained similar results regarding natural delivery rates (15). A considerable increase in natural delivery rates during the COVID-19 pandemic is also mentioned in another study (16). Another study Herein, some limitations and challenges must be considered before applying the findings, including sole investigation of public healthcare centers, short study period, and lack of sufficient information about real causes of abortion.

Conclusion
While rigorous evidence is not available yet, evidence provided by this study indicated the negative impact of the COVID-19 pandemic on referring to healthcare centers to receive antenatal care among pregnant women living in cities with a population of > 20,000. A reverse trend was observed in rural areas and cities with a population of < 20,000. However, this study showed that the COVID-19 pandemic imposes