Maternal Common Cold or Fever During Pregnancy and the Risk of Orofacial Clefts in the Offspring: A Systematic Review and Meta-analysis

Abstract

The common cold and/or an associated fever during pregnancy have/has been suspected to harm the developing fetus. We sought possible correlations between a maternal common cold or fever during pregnancy and the risk of orofacial clefts in the offspring. We systematically searched PubMed and Embase using appropriate keywords, and we checked the reference lists of retrieved articles. We used random-effects models to estimate overall relative risks. Incidence of orofacial clefts. We included 13 case-control studies. Modest but statistically significant associations were found between a maternal common cold and cleft lip with or without a cleft palate (CL/CP) (odds ratio [OR] 2.17; 95% confidence interval [CI] 1.66–2.83) and a cleft palate only (CPO) (OR 3.08; 95% CI 1.5–6.34). Furthermore, maternal fever was also associated with an increased risk of CL/CP (OR 1.91, 95% CI 1.3–2.8) and CPO (OR 1.48, 95% CI 0.83–2.63) in the offspring. Further analyses of maternal influenza (alone) yielded similar results. Although evidence of heterogeneity should be carefully evaluated, our findings suggest that maternal common cold or fever during pregnancy may be associated with a greater risk of CL/CP or CPO in the offspring. Future cohort studies using valid assessments of maternal common cold exposure during pregnancy that consider the severity of fever are needed to clarify the contribution of maternal common cold or fever status to the risk of orofacial clefts in children.

Assessment of non-syndromic orofacial cleft severity and associated environmental factors in Saudi Arabia: A cross-sectional study

“…Furthermore, a greater than threefold increase in AOR was found for the severity of CL ± P or CP with mothers reporting exposure to illnesses in their 3-month pre-gestation and first trimester periods. This increase was also found by studies that reported an increased NSOFC prevalence in mothers exposed to illnesses compared to the prevalence of NSOFC in infants ( Inchingolo et al, 2022 , Shi et al, 2023 ). Pathogens could be vertically transmitted from the mother through the placenta, thereby affecting the developing fetus.…”

“…The etiology of NSOFC is multifactorial, involving both genetic and environmental components, as well as interactions between the two ( Mossey and Modell, 2012 ). Several studies have linked environmental factors, such as socioeconomic status, parental age, consanguinity ( Sabbagh et al, 2014 ), family history, maternal medication use, stress, infections, and maternal nicotine exposure during the 3-month pre-gestation period and the first trimester, to the development of oral clefts ( Lie et al, 1994 , Bille et al, 2005 , Shahrukh Hashmi et al, 2010 , Jia et al, 2011 , Lin et al, 2012 , Carmichael et al, 2014 , Sabbagh et al, 2015a , Sabbagh et al, 2015b , Sabbagh et al, 2016 , Jamilian et al, 2017 , Shi et al, 2023 ). However, few studies have investigated the severity of NSOFC and related environmental risk factors.…”

Evidence Mapping and Quality Analysis of Systematic Reviews on Various Aspects Related to Cleft Lip and Palate

“…These steps resulted in the inclusion of 18 more SRs. Altogether, 144 SRs and MAs [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , ...…”

“…There was an increasing trend in their numbers with time. The maximum number of published articles were from the year 2021 (n = 29) [ 28 , 46 , 47 , 48 , 55 , 61 , 62 , 63 , 64 , 65 , 69 , 76 , 81 , 82 , 99 , 100 , 101 , 102 , 111 , 128 , 129 , 130 , 142 , 143 , 145 , 148 , 153 , 154 , 161 ]. It was observed that only three studies performed before 2010 could qualify during the two-stage scrutiny [ 72 , 112 , 113 ].…”

“…It was observed that only three studies performed before 2010 could qualify during the two-stage scrutiny [ 72 , 112 , 113 ]. Among the journals, the highest number of papers (n = 30) was published in the Cleft Palate Craniofacial Journal (CPCJ) [ 21 , 35 , 46 , 47 , 48 , 49 , 63 , 65 , 66 , 76 , 86 , 92 , 94 , 100 , 101 , 115 , 116 , 121 , 123 , 125 , 128 , 137 , 140 , 142 , 146 , 150 , 152 , 155 , 161 , 162 ] followed by The Cochrane Library (n = 8) [ 9 , 16 , 68 , 88 , 92 , 93 , 100 , 106 ] and the International Journal of Oral and Maxillofacial Surgery (n = 7) [ 31 , 72 , 89 , 93 , 106 , 110 , 135 ]. There was diversity among the journals of different specialties that had published the SRs related to CLP ( Supplementary Material S4 ).…”