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Genetic and Environmental Influences on Maternal, Fetal and Neonatal Diseases

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A special issue of International Journal of Environmental Research and Public Health (ISSN 1660-4601). This special issue belongs to the section "Global Health".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 24535

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Special Issue Editors

Dr. Kazumichi Fujioka

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Guest Editor

Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
Interests: neonatology; perinatal infection; sepsis model; neonatal jaundice
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Hans Van Rostenberghe

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Assistant Guest Editor

Department of Paediatrics, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia
Interests: neonatology; neonatal jaundice; infection prevention; care for the underprivileged

Special Issue Information

Dear Colleagues,

This Special Issue of IJERPH, entitled “Genetic and Environmental Influences on Maternal, Fetal, and Neonatal Diseases”, offers an opportunity to publish high-quality research, reviews, and case series that further the understanding of the roles that the genetics and environment play in maternal, fetal, and neonatal health and well-being.

Despite recent advances in perinatal management, the number of low birth weight infants has been increased, especially in developed countries like Japan. The reason has been suggested to be increased numbers of fetal growth restrictions and preterm births by several recent studies. Both genetic and environmental factors, such as polymorphisms, epigenetics, diet, infections, mental well-being, socioeconomic status, and maternal complications, have been found to influence these perinatal morbidities, which might result in neonatal complications or even lead to neurodevelopmental impairment. In addition, prenatal and perinatal exposures to adverse environmental factors are known to be associated with the development of adult chronic diseases, or developmental origins of health and disease (DOHaD).

Thus, understanding how the various genetic and environmental factors that fetuses and neonates are exposed to affect their health and well-being has gained considerable attention in public health research. Accordingly, the aim of this Special Issue is to highlight the broad scope of novel and contemporary research focused on maternal, fetal, and neonatal health.

We welcome clinical, basic, and epidemiological research. Submissions that discuss new knowledge, developments, and innovations in the field of genetic and environmental determinants of mother and child health are particularly encouraged.

We invite you to submit articles on topics including, but not limited to, the following:

Identification of genetic and environmental factors that affect maternal, fetal, and neonatal health;
Long-term outcome in infants born to mothers with pregnancy complications;
Differences in the environment of mothers and their children between developing and developed countries;
Novel insight into developmental origins of health and disease;
Genetic susceptibility to perinatal diseases;
The impact of psychosocial problems in pregnancy and neonatal outcome;
Cultural differences in breast milk sharing for preterm babies;
Application of evidence-based medicine in the neonatal setting.

Dr. Kazumichi Fujioka
Prof. Dr. Hans Van Rostenberghe
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Environmental Research and Public Health is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2500 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Genetics
Environment
Pregnancy complications
Fetal growth
Neonatal morbidities
Developmental origins of health and disease
Neurodevelopmental outcome
Infections
Socioeconomic status
Breastfeeding

Published Papers (10 papers)

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Research

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9 pages, 811 KiB

Open AccessArticle

Antenatal Corticosteroids to Asian Women Prior to Elective Cesarean Section at Early Term and Effects on Neonatal Respiratory Outcomes

by Noorazizah Arsad, Nurlina Abd Razak, Mohd Hashim Omar, Mohamad Nasir Shafiee, Aida Kalok, Fook Choe Cheah and Pei Shan Lim

Int. J. Environ. Res. Public Health 2022, 19(9), 5201; https://doi.org/10.3390/ijerph19095201 - 25 Apr 2022

Viewed by 2086

Abstract

This exploratory study aimed to evaluate the effects of antenatal corticosteroids in singleton pregnancies of Asian women prior to elective cesarean section (CS) at early term on neonatal respiratory outcomes. Methods: This is a pilot and pragmatic randomized trial conducted at a university hospital in Malaysia. Women with singleton pregnancies planned for elective CS between 37⁺⁰ and 38⁺⁶ weeks gestation were randomly allocated into the intervention group, where they received two doses of IM dexamethasone 12 mg of 12 h apart, 24 h prior to surgery OR into the standard care, control group, and both groups received the normal routine antenatal care. The primary outcome measures were neonatal respiratory illnesses, NICU admission and length of stay. Results: A total of 189 patients were recruited, 93 women in the intervention group and 96 as controls. Between the steroid and control groups, the mean gestation at CS was similar, 266.1 ± 3.2 days (38 weeks) vs. 265.8 ± 4.0 days (37⁺⁶ weeks), p = 0.53. The mean birthweight of infants was 3.06 ± 0.41 kg vs. 3.04 ± 0.37 kg, p = 0.71. Infants with respiratory morbidities were primarily due to transient tachypnea of newborn (9.7% vs. 6.3%), and congenital pneumonia (1.1% vs. 3.1%) but none had respiratory distress syndrome. Only four infants required NICU admission (2.2% vs. 3.1%, p = 0.63). Their average length of stay was not statistically different; 3.5 ± 2.1 days vs. 5.7 ± 1.5 days, p = 0.27. Conclusions: Elective CS at early term before 39 weeks was associated with a modest overall incidence of neonatal respiratory illness (10.1%) in this Asian population. Antenatal dexamethasone did not diminish infants needing respiratory support, NICU admission and length of stay. Full article

(This article belongs to the Special Issue Genetic and Environmental Influences on Maternal, Fetal and Neonatal Diseases)

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8 pages, 1361 KiB

Open AccessArticle

Correlation between Severity of Fetal Growth Restriction and Oxidative Stress in Severe Small-for-Gestational-Age Infants

by Mariko Ashina, Takumi Kido, Yuki Kyono, Asumi Yoshida, Shutaro Suga, Ruka Nakasone, Shinya Abe, Kenji Tanimura, Kandai Nozu and Kazumichi Fujioka

Int. J. Environ. Res. Public Health 2021, 18(20), 10726; https://doi.org/10.3390/ijerph182010726 - 13 Oct 2021

Cited by 6 | Viewed by 1626

Abstract

Severe small-for-gestational-age (sSGA) infants exhibit increased mortality and morbidity. Oxidative stress is suggested to be involved in intrauterine growth restriction. This retrospective study aimed to evaluate the oxidative stress level at birth in an sSGA population. Sera of 28 sSGA (sSGA group) and 31 non-sSGA (control group) infants, born at our hospital between March 2017 and March 2020, were evaluated. Oxidative stress (derivative of reactive oxidative metabolites: d-ROM level), biological antioxidant potential (BAP) level, and the ratio of d-ROM/BAP level (oxidative stress index: OSI) were measured. The sSGA group had a significantly lower birth weight (BW), BW z-score, head circumference, and height than the control group (all p < 0.05). No significant difference was noted in the BAP level; sSGA infants exhibited a significantly higher d-ROM level than control infants. sSGA infants showed a significantly increased OSI compared with control infants, and the BW z-score was inversely correlated with d-ROM levels and OSI in sSGA infants (R² = 0.300; p < 0.01 and R² = 0.319; p = 0.02, respectively) but not in controls. In conclusion, sSGA infants, including preterm infants, exhibited higher oxidative stress at birth. The severity of fetal growth restriction was significantly correlated with oxidative stress levels at birth in sSGA infants. Full article

(This article belongs to the Special Issue Genetic and Environmental Influences on Maternal, Fetal and Neonatal Diseases)

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9 pages, 799 KiB

Open AccessArticle

Haemoglobin Levels in Early Life among Infants with and without Retinopathy of Prematurity

by Edwin Pheng, Zi Di Lim, Evelyn Tai Li Min, Hans Van Rostenberghe and Ismail Shatriah

Int. J. Environ. Res. Public Health 2021, 18(13), 7054; https://doi.org/10.3390/ijerph18137054 - 1 Jul 2021

Cited by 4 | Viewed by 1925

Abstract

Retinopathy of prematurity (ROP) is a proliferative retinal vascular disorder attributed to an ischaemic stimulus in preterm infants. Haemoglobin, the main component for oxygen transportation, may be implicated in ROP development. This retrospective study compared the mean weekly haemoglobin levels between infants with and without ROP over the first six weeks of life. Premature infants of less than 32 weeks gestational age and less than 1.5 kg birth weight were grouped into age and birth weight-matched ROP cases and controls. Weekly mean haemoglobin levels were documented. An independent t-test was used to analyze the difference in mean haemoglobin levels between infants with ROP and infants without ROP. Adjustment for confounders was performed using one-way analysis of covariance. There was a statistically significant difference in adjusted mean haemoglobin levels between the ROP and non-ROP group during the first week of life (p = 0.038). No significant intergroup differences were observed at the other weeks. Haemoglobin monitoring during the first week of postnatal life may be useful to guide ROP screening in premature infants. Full article

(This article belongs to the Special Issue Genetic and Environmental Influences on Maternal, Fetal and Neonatal Diseases)

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12 pages, 604 KiB

Open AccessArticle

Phthalate Exposure Pattern in Breast Milk within a Six-Month Postpartum Time in Southern Taiwan

by Shen-Che Hung, Ting-I Lin, Jau-Ling Suen, Hsien-Kuan Liu, Pei-Ling Wu, Chien-Yi Wu, Yu-Chen S. H. Yang, San-Nan Yang and Yung-Ning Yang

Int. J. Environ. Res. Public Health 2021, 18(11), 5726; https://doi.org/10.3390/ijerph18115726 - 26 May 2021

Cited by 7 | Viewed by 2833

Abstract

Di-(2-ethylhexyl) phthalate (DEHP), a common plasticizer, has been detected in breast milk in many countries; however, whether phthalate metabolite concentration and the detection rate in breast milk change postpartum is still unknown. We measured phthalate metabolite concentrations in breast milk in the first 6 months postpartum in women enrolled in the E-Da hospital from January to July 2017. A total of 56 breastfeeding mothers and 66 samples were included in this study. We analyzed the samples’ concentration of eight phthalate metabolites using liquid chromatography mass spectrometry. The concentration of mono-2-ethylhexyl phthalate (MEHP) was significantly higher in the first month, and then decreased over time. The detection rate of ono-isobutyl phthalate (MiBP) and mono-n-butyl phthalate (MBP) was low in the first month and then increased over time. Compared with a previous study published in 2011, the levels of MEHP and MiBP in breast milk were much lower in the present study, suggesting an increased awareness of the health risks of phthalate exposure after a food scandal occurred in Taiwan. This study provides information for evaluating newborns’ exposure to different kinds of phthalate through human milk in the postpartum period. Full article

(This article belongs to the Special Issue Genetic and Environmental Influences on Maternal, Fetal and Neonatal Diseases)

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8 pages, 450 KiB

Open AccessArticle

A Randomized Controlled Trial Comparing Two Doses of Caffeine for Apnoea in Prematurity

by Anis Munirah Mohd Kori, Hans Van Rostenberghe, Nor Rosidah Ibrahim, Najib Majdi Yaacob and Ariffin Nasir

Int. J. Environ. Res. Public Health 2021, 18(9), 4509; https://doi.org/10.3390/ijerph18094509 - 23 Apr 2021

Cited by 9 | Viewed by 2764

Abstract

Caffeine is the most commonly used methyl xanthine for the prevention of apnoea in prematurity, but the ideal dose was uncertain, until now. This study compared two doses of caffeine for the prevention of apnoea in prematurity. A clinical trial was conducted on 78 preterm infants ≤32 weeks in Neonatal Intensive Care Unit. They were randomly allocated to receive the intervention (loading 40 mg/kg/day and maintenance of 20 mg/kg/day) or the control (loading 20 mg/kg/day and maintenance of 10 mg/kg/day) dose of caffeine. The primary outcome of the study was the frequency and total days of apnoea per duration of treatment for both groups. The frequency of apnoea ranged from zero to fourteen in the intervention group and zero to twelve in the control group. There was no statistically significant difference between the groups, with a p-value of 0.839. The number of days of apnoea was also similar between both groups, with a p-value of 0.928. There was also no significant difference in adverse events between both regimens. This study did not support the use of higher doses of caffeine as a prevention for apnoea in prematurity. Full article

(This article belongs to the Special Issue Genetic and Environmental Influences on Maternal, Fetal and Neonatal Diseases)

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9 pages, 847 KiB

Open AccessArticle

Comparison of Mean Platelet Counts in Preterm Infants with and without Retinopathy of Prematurity

by Zi Di Lim, Edwin Pheng, Evelyn Tai Li Min, Hans Van Rostenberghe and Ismail Shatriah

Int. J. Environ. Res. Public Health 2021, 18(7), 3783; https://doi.org/10.3390/ijerph18073783 - 5 Apr 2021

Cited by 3 | Viewed by 2154

Abstract

Platelets are a primary source of pro- and anti-angiogenic cytokines. However, the evidence of their role in retinopathy of prematurity (ROP) is controversial. This retrospective study aimed to compare mean weekly platelet counts between infants with and without ROP over the first 6 weeks of life. A total of 93 infants matched by gestational age and birth weight were recruited (31 with ROP, 62 without ROP). Weekly mean platelet counts and other related risk factors were documented. The repeated measure analysis of variance (ANOVA) and the repeated measure analysis of covariance (ANCOVA) were used to compare mean platelet counts over time between the two groups, with and without adjusting for confounders. We found significant differences in the weekly mean platelet counts of infants with and without ROP over the first 6 weeks of life (p = 0.002). These differences disappeared after adjusting for covariates (p = 0.489). Lower mean platelet counts in ROP infants are not directly related to ROP, but rather to the presence of other risk factors for ROP, such as culture-proven sepsis, blood transfusion and bronchopulmonary dysplasia. Full article

(This article belongs to the Special Issue Genetic and Environmental Influences on Maternal, Fetal and Neonatal Diseases)

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24 pages, 1946 KiB

Open AccessArticle

Is Handedness at Five Associated with Prenatal Factors?

by Jacqueline Fagard, Maria De Agostini, Viviane Huet, Lionel Granjon and Barbara Heude

Int. J. Environ. Res. Public Health 2021, 18(7), 3529; https://doi.org/10.3390/ijerph18073529 - 29 Mar 2021

Cited by 5 | Viewed by 2270

Abstract

The goal of the study was to investigate some of the factors suspected to be related to children’s handedness: presentation during the last weeks of gestation and at birth (cephalic or breech), side of presentation (right or left), number of weeks of gestation, season of birth, parents’ handedness and sex. We analyzed the relationships between these factors and the child’s handedness at five years. Children (n = 1897) from the EDEN cohort participated in the study, among which 1129 were tested for handedness at five. The father’s handedness, but not the mother’s, was significantly related to the child’s hand preference. The percentage of left-handed children was significantly larger when the father was non-right-handed compared to right-handed, and tended to be larger among children in non-left-cephalic presentation compared to left-cephalic presentation. Girls, but not boys, were significantly less lateralized when they were born before 37 weeks of pregnancy than after. Finally, children born in winter or spring were slightly but significantly less lateralized than children born in summer or autumn. All six children who were not lateralized at 5 presented one or several of these factors. These results are discussed in light of the mixed model of handedness. Full article

(This article belongs to the Special Issue Genetic and Environmental Influences on Maternal, Fetal and Neonatal Diseases)

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11 pages, 476 KiB

Open AccessArticle

Neurodevelopmental Outcomes at 18 Months of Corrected Age for Late Preterm Infants Born at 34 and 35 Gestational Weeks

by Ruka Nakasone, Kazumichi Fujioka, Yuki Kyono, Asumi Yoshida, Takumi Kido, Shutaro Suga, Shinya Abe, Mariko Ashina, Kosuke Nishida, Kenji Tanimura, Hideto Yamada, Kandai Nozu and Kazumoto Iijima

Int. J. Environ. Res. Public Health 2021, 18(2), 640; https://doi.org/10.3390/ijerph18020640 - 13 Jan 2021

Cited by 4 | Viewed by 2365

Abstract

To date, the difference in neurodevelopmental outcomes between late preterm infants (LPI) born at 34 and 35 gestational weeks (LPI-34 and LPI-35, respectively) has not been elucidated. This retrospective study aimed to evaluate neurodevelopmental outcomes at 18 months of corrected age for LPI-34 and LPI-35, and to elucidate factors predicting neurodevelopmental impairment (NDI). Records of all LPI-34 (n = 93) and LPI-35 (n = 121) admitted to our facility from 2013 to 2017 were reviewed. Patients with congenital or chromosomal anomalies, severe neonatal asphyxia, and without developmental quotient (DQ) data were excluded. Psychomotor development was assessed as a DQ using the Kyoto Scale of Psychological Development at 18 months of corrected age. NDI was defined as DQ < 80 or when severe neurodevelopmental problems made neurodevelopmental assessment impossible. We compared the clinical characteristics and DQ values between LPI-34 (n = 62) and LPI-35 (n = 73). To elucidate the factors predicting NDI at 18 months of corrected age, we compared clinical factors between the NDI (n = 17) and non-NDI (n = 118) groups. No significant difference was observed in DQ values at 18 months of corrected age between the groups in each area and overall. Among clinical factors, male sex, intraventricular hemorrhage (IVH), hyperbilirubinemia, and severe hyperbilirubinemia had a higher prevalence in the NDI group than in the non-NDI group, and IVH and/or severe hyperbilirubinemia showed the highest Youden Index values for predicting NDI. Based on the results of this study, we can conclude that no significant difference in neurodevelopmental outcomes at 18 months of corrected age was observed between LPI-34 and LPI-35. Patients with severe hyperbilirubinemia and/or IVH should be considered to be at high risk for developing NDI. Full article

(This article belongs to the Special Issue Genetic and Environmental Influences on Maternal, Fetal and Neonatal Diseases)

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11 pages, 335 KiB

Open AccessReview

The Role of Heme Oxygenase-1 Promoter Polymorphisms in Perinatal Disease

by Ruka Nakasone, Mariko Ashina, Shinya Abe, Kenji Tanimura, Hans Van Rostenberghe and Kazumichi Fujioka

Int. J. Environ. Res. Public Health 2021, 18(7), 3520; https://doi.org/10.3390/ijerph18073520 - 29 Mar 2021

Cited by 9 | Viewed by 2690

Abstract

Heme oxygenase (HO) is the rate-limiting enzyme in the heme catabolic pathway, which degrades heme into equimolar amounts of carbon monoxide, free iron, and biliverdin. Its inducible isoform, HO-1, has multiple protective functions, including immune modulation and pregnancy maintenance, showing dynamic alteration during perinatal periods. As its contribution to the development of perinatal complications is speculated, two functional polymorphisms of the HMOX1 gene, (GT)_n repeat polymorphism (rs3074372) and A(-413)T single nucleotide polymorphism (SNP) (rs2071746), were studied for their association with perinatal diseases. We systematically reviewed published evidence on HMOX1 polymorphisms in perinatal diseases and clarified their possible significant contribution to neonatal jaundice development, presumably due to their direct effect of inducing HO enzymatic activity in the bilirubin-producing pathway. However, the role of these polymorphisms seems limited for other perinatal complications such as bronchopulmonary dysplasia. We speculate that this is because the antioxidant or anti-inflammatory effect is not directly mediated by HO but by its byproducts, resulting in a milder effect. For better understanding, subtyping each morbidity by the level of exposure to causative environmental factors, simultaneous analysis of both polymorphisms, and the unified definition of short and long alleles in (GT)_n repeats based on transcriptional capacity should be further investigated. Full article

(This article belongs to the Special Issue Genetic and Environmental Influences on Maternal, Fetal and Neonatal Diseases)

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7 pages, 1548 KiB

Open AccessCase Report

A Preterm Case of Cow’s Milk Allergy Presenting with Recurrent Ascites Treated with Donor Breast Milk

by Ruka Nakasone, Kazumichi Fujioka, Shutaro Suga, Shinya Abe, Mariko Ashina, Kosuke Nishida, Motoichiro Sakurai, Katsumi Mizuno, Kandai Nozu and Kazumoto Iijima

Int. J. Environ. Res. Public Health 2021, 18(3), 1187; https://doi.org/10.3390/ijerph18031187 - 29 Jan 2021

Cited by 2 | Viewed by 2736

Abstract

We report a case of a preterm infant who developed cow’s milk allergy. This male infant presented with recurrent ascites and was successfully treated with donated breast milk. He was born at 24 weeks’ gestation with a birthweight of 506 g. From day 20, infant formula, soy protein-based formula, and casein-hydrolyzed formula were used due to insufficient maternal lactation. This resulted in abdominal distention, generalized edema, and recurrent ascites. We diagnosed him with cow’s milk allergy since these symptoms improved on exclusive breast milk feeding. No recurrence of symptoms occurred when donated breast milk was used in combination with the mother’s own milk. Ascites should be regarded as a clinical symptom of neonatal cow’s milk allergy. Donated breast milk may be effective in the treatment of the allergy if breastfeeding is not available. Full article

(This article belongs to the Special Issue Genetic and Environmental Influences on Maternal, Fetal and Neonatal Diseases)

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