Prevalence of congenital microcephaly and its risk factors in an area at risk of Zika outbreaks

Shen, Shi‐Li; Xiao, Wan-Qing; Zhang, Lifang; Lu, Jinhua; Funk, Anna; He, Jianxing; Tu, Si; Yu, Jia-Kuo; Yang, Li; Fontanet, Arnaud; Bao, Wei; Cheng, Kar Keung; Qiu, Xiu

doi:10.1186/s12884-021-03705-9

Cited by 8 publications

(8 citation statements)

References 42 publications

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“…It was also 1.5 times higher than reported in Brazil (60 cases per 10,000 births) at the peak of the ZIKV outbreak in 2016. However, a study in China reported a higher prevalence of 410 cases per 10,000 births [ 30 ]. None of the newborns with microcephaly in our study had evidence of ZIKV and only one had confirmed DENV exposure.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of microcephaly and Zika virus infection in a pregnancy cohort in Kenya, 2017–2019

Osoro

Inwani

Mugo

et al. 2022

BMC Med

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Background Zika virus (ZIKV), first discovered in Uganda in 1947, re-emerged globally in 2013 and was later associated with microcephaly and other birth defects. We determined the incidence of ZIKV infection and its association with adverse pregnancy and fetal outcomes in a pregnancy cohort in Kenya. Methods From October 2017 to July 2019, we recruited and followed up women aged ≥ 15 years and ≤ 28 weeks pregnant in three hospitals in coastal Mombasa. Monthly follow-up included risk factor questions and a blood sample collected for ZIKV serology. We collected anthropometric measures (including head circumference), cord blood, venous blood from newborns, and any evidence of birth defects. Microcephaly was defined as a head circumference (HC) < 2 standard deviations (SD) for sex and gestational age. Severe microcephaly was defined as HC < 3 SD for sex and age. We tested sera for anti-ZIKV IgM antibodies using capture enzyme-linked immunosorbent assay (ELISA) and confirmed positives using the plaque reduction neutralization test (PRNT90) for ZIKV and for dengue (DENV) on the samples that were ZIKV neutralizing antibody positive. We collected blood and urine from participants reporting fever or rash for ZIKV testing. Results Of 2889 pregnant women screened for eligibility, 2312 (80%) were enrolled. Of 1916 recorded deliveries, 1816 (94.6%) were live births and 100 (5.2%) were either stillbirths or spontaneous abortions (< 22 weeks of gestation). Among 1236 newborns with complete anthropometric measures, 11 (0.9%) had microcephaly and 3 (0.2%) had severe microcephaly. A total of 166 (7.2%) participants were positive for anti-ZIKV IgM, 136 of whom became seropositive during follow-up. Among the 166 anti-ZIKV IgM positive, 3 and 18 participants were further seropositive for ZIKV and DENV neutralizing antibodies, respectively. Of these 3 and 18 pregnant women, one and 13 (72.2%) seroconverted with antibodies to ZIKV and DENV, respectively. All 308 samples (serum and urine samples collected during sick visits and samples that were anti-ZIKV IgM positive) tested by RT-PCR were negative for ZIKV. No adverse pregnancy or neonatal outcomes were reported among the three participants with confirmed ZIKV exposure. Among newborns from pregnant women with DENV exposure, four (22.2%) were small for gestational age and one (5.6%) had microcephaly. Conclusions The prevalence of severe microcephaly among newborns in coastal Kenya was high relative to published estimates from facility-based studies in Europe and Latin America, but little evidence of ZIKV transmission. There is a need for improved surveillance for microcephaly and other congenital malformations in Kenya.

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Section: Discussionmentioning

confidence: 99%

Prevalence of microcephaly and Zika virus infection in a pregnancy cohort in Kenya, 2017–2019

Osoro

Inwani

Mugo

et al. 2022

BMC Med

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“…The two cities, Quebec and Guangzhou, had no documented evidence of ZIKV infection at the time these studies took place [ 26 , 27 ]. A second study in Guangzhou included 46,610 live births between 2017–2018 and identified 154 microcephaly cases [ 28 ]. The authors showed that maternal hepatitis B virus infection, primiparous mothers, preterm labor, and fetal growth restriction were main drivers of microcephaly cases [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…A second study in Guangzhou included 46,610 live births between 2017–2018 and identified 154 microcephaly cases [ 28 ]. The authors showed that maternal hepatitis B virus infection, primiparous mothers, preterm labor, and fetal growth restriction were main drivers of microcephaly cases [ 28 ]. Although it was the first time that maternal exposure to congenital hepatitis B virus infection has been associated with microcephaly [ 28 ], the strength of its effect on microcephaly risk ( RR = 1.62) is lower than the risks from maternal infection by TORCH ( RR = 4.29–31.17), as shown by [ 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…( A ) Socioeconomic, ( B ) Teratogen, ( C ) TORCH, ( D ) ZIKV. A1 = Campos et al, 2018 [ 24 ]; A2 = Silva et al, 2018 [ 25 ]; B1 = Auger et al, 2018 [ 26 ]; B2 = Liu et al, 2019 [ 27 ]; C1 = Auger et al, 2018 [ 26 ]; C2 = Liu et al, 2019 [ 27 ]; C3 = Shen et al, 2021 [ 28 ]; C4 = Messinger et al, 2020 [ 29 ]; D1 = Mendes et al, 2020 [ 30 ]; D2 = Robbiani et al, 2019 [ 31 ]; D3 = Barsosio et al, 2019 [ 32 ].…”

Section: Figurementioning

confidence: 99%

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Microcephaly and Associated Risk Factors in Newborns: A Systematic Review and Meta-Analysis Study

2022

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Congenital microcephaly is caused by a multitude of drivers affecting maternal–fetal health during pregnancy. It is a rare outcome in high-income industrial countries where microcephaly rates are in the range of 0.3–0.9 per 1000 newborns. Prevalence of microcephaly varies considerably across developing countries and can go as high as 58 cases per 1000 live births in pregnancies exposed to infection by Zika virus (ZIKV). Not only ZIKV-infected pregnancies, but other drivers can modulate the occurrence and severity of this outcome. Here, we sought to test the ZIKV–microcephaly association vs. competing hypotheses using a meta-analysis with 8341 microcephaly cases pooled from 10,250,994 newborns in the Americas, Africa, and Asia. Analysis of risk ratios (RR) showed teratogens the most likely microcephaly-associated risk factor (RR = 3.43; 95%-CI 2.69–4.38; p-value < 0.0001), while the statistical significance of the ZIKV–microcephaly association was marginal (RR = 2.12; 95%-CI 1.01–4.48; p-value = 0.048). Other congenital infections showed strong but variable associations with microcephaly (RR = 15.24; 95%-CI 1.74–133.70; p-value = 0.014). Microcephaly cases were associated with impoverished socioeconomic settings, but this association was statistically non-significant (RR = 2.75; 95%-CI 0.55–13.78; p-value = 0.22). The marginal ZIKV–microcephaly association and statistical significance of the competing hypotheses suggest maternal ZIKV infection might not be a cause of microcephaly alone.

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“…Congenital microcephaly (CM) is defined as having an occipitofrontal circumference (OFC) that is more than two standard deviations (SDs) below the mean at birth for gestational age and sex [1, 2]; and the prevalence is reported to be 1–33 per 10,000 live births [3, 4]. Neurological abnormalities are usually associated with CM [5, 6].…”

Section: Introductionmentioning

confidence: 99%

Molecular Genetic Analysis of Newborns with Congenital Microcephaly

Mei

Chen

et al. 2022

Neonatology

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Introduction: Data on the genetic landscape of congenital microcephaly (CM) in China are scarce, and the incidence of CM caused by the most commonly mutated gene ASPM in China remains unknown. Methods: Sixty-one neonates with CM who were hospitalized in the Children’s Hospital of Fudan University between August 1, 2016, and August 31, 2020, were enrolled, and the clinical data and clinical exome-sequencing data were analyzed. An additional 18,103 parental data entries from the Chinese Children’s Genetic Testing Clinical Collaboration System database were collected to estimate the incidence of ASPM-related congenital microcephaly (ASPM-CM) in East China by analyzing the carrier frequency of ASPM mutations. Results: Among the 61 neonates with CM, 35 (57.4%) patients were identified with genetic findings, including 24 patients with single nucleotide variants (SNVs) and 11 patients with copy number variations (CNVs). ASPM was the most common gene with detrimental SNVs detected in 3 patients. Patients with genetic findings showed a significantly higher incidence of developmental delay (91.3%, 21/23) than those without genetic findings (60%, 9/15) (p = 0.04). All the 3 decreased patients had genetic findings. The estimated ASPM-CM incidence in East China was 1/1,295,044. Conclusion: Comprehensive genetic testing, detecting both SNVs and CNVs, is recommended for newborns with CM. Patients with genetic findings should be aware of the potential for developmental delay. ASPM gene defect was the most common genetic cause of CM in this study. The estimation of the incidence of ASPM-CM in East China might provide a reference for analyzing overall incidence.

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Prevalence of congenital microcephaly and its risk factors in an area at risk of Zika outbreaks

Cited by 8 publications

References 42 publications

Prevalence of microcephaly and Zika virus infection in a pregnancy cohort in Kenya, 2017–2019

Prevalence of microcephaly and Zika virus infection in a pregnancy cohort in Kenya, 2017–2019

Microcephaly and Associated Risk Factors in Newborns: A Systematic Review and Meta-Analysis Study

Molecular Genetic Analysis of Newborns with Congenital Microcephaly

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