Sexual origins of placental dysfunction

doi:10.1016/S0140-6736(99)05061-8

The Lancet

Volume 355, Issue 9199, 15 January 2000, Pages 203-204

https://doi.org/10.1016/S0140-6736(99)05061-8 Get rights and content

Summary

Severe placental dysfunction is much more common in pregnancies with a male than with a female fetus. Furthermore, the birthweight/placental weight ratio is increased in these pregnancies, consistent with fetal growth restriction, and is higher with a male fetus than with a female fetus. These observations of placental insufficiency may underlie the increased in-utero loss rate of male fetuses.

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Cited by (63)

Placental accelerated aging in antenatal depression
2024, American Journal of Obstetrics and Gynecology MFM
Antenatal maternal depression is associated with poor pregnancy outcomes and long-term effects on the offspring. Previous studies have identified links between antenatal depression and placental DNA methylation and between placental epigenetic aging and poor pregnancy outcomes, such as preterm labor and preeclampsia. The relationship between antenatal depression and poor pregnancy outcomes may be partly mediated via placental aging.
This study aimed to investigate whether antenatal depressive symptoms are associated with placental epigenetic age acceleration, an epigenetic aging clock measure derived from the difference between methylation age and gestational age at delivery.
The study included 301 women who provided placenta samples at delivery as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies – Singletons that recruited participants from diverse race and ethnic groups at 12 US clinical sites (2009–2013). Women underwent depression screening using the Edinburgh Postnatal Depression Scale up to 6 times across the 3 trimesters of pregnancy. Depressive symptoms status was determined for each pregnancy trimester using an Edinburgh Postnatal Depression Scale score, in which a score of ≥10 was defined as having depressive symptoms and a score of <10 was defined as not having depressive symptoms. Placental DNA methylation was profiled from placenta samples. Placental epigenetic age was estimated using a methylation-based age estimator (placental “epigenetic clock”) that has previously been found to have high placental gestational age prediction accuracy for uncomplicated term pregnancies. Placental age acceleration was defined to be the residual upon regressing the estimated epigenetic age on gestational age at delivery. Associations between an Edinburgh Postnatal Depression Scale score of ≥10 and an Edinburgh Postnatal Depression Scale score of <10 in the first, second, and third trimesters of pregnancy (ie, depressive symptoms vs none in each trimester) and placental age acceleration were tested using multivariable linear regression adjusting for maternal age, parity, race and ethnicity, and employment.
There were 31 (10.3%), 48 (16%), and 49 (16.4%) women with depressive symptoms (ie, Edinburgh Postnatal Depression Scale score of ≥10) in the first, second, and third trimesters of pregnancy, respectively. Of these women, 21 (7.2%) had sustained first- and second-trimester depressive symptoms, 19 (7%) had sustained second- and third-trimester depressive symptoms, and 12 (4.8%) had sustained depressive symptoms throughout pregnancy. Women with depressive symptoms in the second trimester of pregnancy had 0.41 weeks higher placental age acceleration than women without depressive symptoms during the second trimester of pregnancy (β=0.21 weeks [95% confidence interval, −0.17 to 0.58; P=.28] during the first trimester of pregnancy; β=0.41 weeks [95% confidence interval, 0.10–0.71; P=.009] during the second trimester of pregnancy; β=0.17 weeks [95% confidence interval, −0.14 to 0.47; P=.29] during the third trimester of pregnancy). Sustained first- and second-trimester depressive symptoms were associated with 0.72 weeks higher placental age acceleration (95% confidence interval, 0.29–1.15; P=.001) than no depressive symptom in the 2 trimesters. The association between second-trimester depressive symptoms and higher placental epigenetic age acceleration strengthened in the analysis of pregnancies with male fetuses (β=0.53 weeks; 95% confidence interval, 0.06–1.08; P=.03) but was not significant in pregnancies with female fetuses.
Antenatal depressive symptoms during the second trimester of pregnancy were associated with an average of 0.41 weeks of increased placental age acceleration. Accelerated placental aging may play an important role in the underlying mechanism linking antenatal depression to pregnancy complications related to placental dysfunction.
The association between female newborn and placental malaria infection: A case-control study
2023, Placenta
There are few published data on the influence of the sex of the fetus or the newborn on the rate of malaria infection. Moreover, the results of these studies are not conclusive. This study was conducted to investigate the association between sex of the newborn and placental malaria infection.
A case-control study was conducted at Al Jabalian maternity hospital in central Sudan during the rainy and post rainy seasons from May to December 2020. The cases were women who had placental malaria, while the controls were subsequent women who had no placental malaria. A questionnaire was filled out by each woman in the case and control groups in order to gather demographic data as well as medical and obstetric history. Malaria was diagnosed using blood films. Logistic regression analyses were performed.
There were 678 women in each arm of the study. Compared with the women without placental malaria (controls), women with placental malaria had a significantly lower age and parity. A significantly higher number of the cases had delivered female newborns, 453 (66.8%) vs. 208 (30.7%), P < 0.001. In logistic regression, women with placental malaria: lived in rural areas, had low antenatal attendance, did not use bed nets, and had more female newborns (adjusted odds ratio, AOR = 2.90, 95% CI = 2.08–4.04).
Women who delivered female were more likely to have placental malaria. Further research into the immunologic and biochemical parameters is warranted.
Maternal Exposure to Air Pollution Is Associated with Neonatal Jaundice: A Retrospective Cohort Study
2022, Journal of Pediatrics
To evaluate the association between maternal ambient pollutant exposure and neonatal jaundice in multiple pollutant species and examine sex differences.
Epidemiologic study: Records of 13 297 newborns (6153 male, 7144 female) born in Taichung, Taiwan were obtained from a national database. Average concentrations of prenatal air pollutants 3 months prior to birth were divided into low, middle, and high levels. Neonatal jaundice phototherapy rates between mothers who suffered varying air pollutant levels were compared. Clinical study: Three hundred seventy-six newborns (189 male, 187 female) born and received jaundice treatment with phototherapy in a hospital in Taichung, Taiwan were recruited. The correlation between prenatal exposure to air pollutants 3 months prior to birth, newborn's serum bilirubin, and serum hemoglobin were calculated.
Epidemiologic study: Male newborns born to mothers exposed to high carbon monoxide (CO), nitric oxide (NO), nitrogen dioxide (NO₂), and methane (CH₄) levels had higher phototherapy rates. In female newborns, the same was noted for CO and CH₄. Clinical study: Male newborns had a positive correlation between CO, ≤2.5 μm diameter particles, ≤10 μm diameter particles, NO, NO₂, nonmethane hydrocarbon, and CH₄ exposure 3 months prior to birth and serum bilirubin levels. Female newborns had a positive correlation for CH₄. A positive correlation between CO, ≤2.5 μm diameter particles, ≤10 μm diameter particles, NO₂, nonmethane hydrocarbon, CH₄ exposure, and serum hemoglobin levels was noted in male newborns.
Maternal exposure to air pollutants may increase neonatal jaundice treatment rates for phototherapy and higher neonatal serum total bilirubin level. Higher hemoglobin levels because of higher pollutant exposures may explain our findings. The association was more obvious in male newborns.
The association of the prothrombin G20210A single-nucleotide polymorphism and the risk of preeclampsia: Systematic review and meta-analysis
2020, European Journal of Obstetrics and Gynecology and Reproductive Biology
We conducted this systematic review and meta-analysis to assess the association between the risk of preeclampsia and the prothrombin G20210A single-nucleotide polymorphism.
We followed the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” guidelines. Relevant published studies were searched in the data base. The retrieved studies were assessed for quality by using the Modified Newcastle-Ottawa Scale for quality assessment. OpenMeta Analyst software was used for the statistics.
Twenty-eight case–control studies enrolling 3821 cases and 4808 controls were included in this systematic review and meta-analysis. We found a significantly increased preeclampsia risk associated with the G20210A polymorphism in three models: allele contrast (A vs. G), OR 2.183, 95 % CI 1.665–2.862; heterozygote (AG vs. GG), OR 2.233, 95 % CI 1.690–2.95; and the dominant model (AA + AG vs. GG) OR 2.240, 95 % CI 1.700–2.950. However, the association was not observed in the homozygote (AA vs. GG) OR 1.310, 95 % CI = 0.632–2.713 r recessive model (AA vs. AG + GG), OR 1.315, 95 % CI = 0.642–2.695.
In this meta-analysis, the prothrombin G20210A single-nucleotide polymorphism was associated with an increased risk of preeclampsia.
Global prevalence of congenital malaria: A systematic review and meta-analysis
2020, European Journal of Obstetrics and Gynecology and Reproductive Biology
Citation Excerpt :
While stable malaria transmission is defined if there is steady prevalence pattern, with minimum variation from one year to another, unstable malaria transmission means large variation in incidence patterns from one year to another [37] (Supplementary file 1). The software “OpenMeta Analyst” for Windows [38,39] was used to perform all the meta-analyses of prevalence of congenital malaria. The Cochrane Q and the I2 were used to evaluate the heterogeneity of the included studies.
The aim of this systematic review and meta-analysis is to pool the prevalence of congenital malaria.
The guideline of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was strictly followed. The published studies were searched in international and national databases. Quality assessment for studied was performed using the modified Newcastle - Ottawa scale. Pooled Meta logistic regression was computed using OpenMeta Analyst software. The heterogeneity was explored by the subgroup and meta-regression method.
Twenty-four studies enrolling 8148 newborns were conducted. All the studies were high-quality studies. The prevalence of congenital malaria ranged from 0.0 % in Colombia to 46.7 % in Nigeria. The overall prevalence of congenital malaria was 6.9 % (95 % CI: 4.8–7.9 %) (562/8148). There was large heterogeneity in prevalence of congenital malaria estimates among the different settings (I² = 96.1 %). Hence the random effect model was used.
In subgroup analyses, with respect to the type of malaria transmission, the prevalence of congenital malaria was significantly higher in areas characterized by unstable malaria transmission vs. the rate in areas with stable malaria transmission [16.8 % (95 % CI: 8.0–25.6 %) vs. 3.5 % (95 % CI: 2.3–4.6 %), Coefficient = 0.111; P = 0.035]. The results of additional sub- group (meta-regression) analyses showed a non-significant difference in prevalence of congenital malaria in study-sample sizes (Coefficient = −0.001, 95 % CI: −0.001 to 0.001), P-value = 0.534) and year of publication (C = −0.005; 95 % CI: −0.016 to 0.006), P-value = 0.369).
This meta-analysis showed a varied prevalence of congenital malaria across endemic areas and it was higher in areas with unstable malaria transmissions.
Birth weight to placenta weight ratio and its relationship to ultrasonic measurements, maternal and neonatal morbidity: A prospective cohort study of nulliparous women
2018, Placenta
Citation Excerpt :
We also found that BWPW-ratio was higher in male infants compared to female infants, suggesting a higher nutrient transfer per gram of placenta in male infants. This has also been described by other studies where it was hypothesized that males prioritize body growth and invest less in placental growth, thereby making them more vulnerable to become undernourished [26–30]. In addition, our results showed that there was no difference in birth weight and the proportion of SGA, AGA and LGA infants across the groups of low, normal and high BWPW-ratio (quintiles Q1, Q2-Q4 and Q5).
Birth weight to placenta weight (BWPW)-ratio is an indicator of the ability of the placenta to maintain adequate nutrient supply to the fetus. We sought to investigate the relationship between BWPW-ratio with fetal growth, utero-placental Doppler and neonatal and maternal morbidity.
We studied a group of 3311 women recruited to a prospective cohort study of nulliparous women (Rosie Hospital, Cambridge, UK) who delivered a live born infant at term and whose placental weight and birth weight were known. Ultrasonic indices and BWPW ratio were converted to gestational age adjusted z scores. Analysis of continuous variables was by multivariable linear regression. BWPW ratio was also categorized (lowest or highest quintile, both referent to quintiles 2 to 4) and associations with adverse outcomes analyzed using multivariable logistic regression.
Lowest quintile of BWPW-ratio was associated (adjusted odds ratio [95% CI], P) with both neonatal morbidity (1.55 [1.12–2.14], 0.007) and maternal diabetes (1.75 [1.18–2.59], 0.005). Highest quintile of BWPW ratio was associated with a reduced risk of maternal obesity (0.71 [0.53 to 0.95], 0.02) and preeclampsia (0.51 [0.31 to 0.84], 0.008), but higher (adjusted z score [95% CI], P) uterine artery Doppler mean pulsatility index (PI) at 20 weeks of gestation (0.09 [0.01–0.18], 0.04) and umbilical artery Doppler PI at 36 weeks of gestation (0.16 [0.07–0.25], <0.001).
BWPW-ratio is related to ultrasonic measurements and both neonatal and maternal morbidity. Therefore, this ratio may be an indicative marker of immediate and longer term health risks for an individual.

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Research LettersSexual origins of placental dysfunction

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Lancet

Placenta

Research Letters
Sexual origins of placental dysfunction