The complement system, a part of the innate immune system, can be activated via three different pathways. In the alternative pathway, a factor D (FD) plays essential roles in both the initiation and the amplification loop and circulates as an active form. Mannose-binding lectin–associated serine proteases (MASPs) are key enzymes of the lectin pathway, and MASP-1 and/or MASP-3 are reported to be involved in the activation of FD. In the current study, we generated mice monospecifically deficient for MASP-1 or MASP-3 and found that the sera of the MASP-1–deficient mice lacked lectin pathway activity, but those of the MASP-3–deficient mice lacked alternative pathway activity with a zymogen FD. Furthermore, the results indicate that MASP-3 but not MASP-1 activates the zymogen FD under physiological conditions and MASP-3 circulates predominantly as an active form. Therefore, our study illustrates that, in mice, MASP-3 orchestrates the overall complement reaction through the activation of FD.
Background: Determining the appropriate preconception care to reduce the occurrence of hypertensive disorder of pregnancy (HDP) remains a challenge in modern obstetrics. This study aimed to examine the association between pre-pregnancy calcium (Ca) intake and HDP in normotensive primiparas. Methods: We used data from the Japan Environment Children's study (JECS), which is the largest birth cohort study. A total of 33,894 normotensive Japanese primiparas were recruited for JECS between January 2011 and March 2014. Participants were categorized into five groups according to pre-pregnancy Ca intake quintiles (Q1 and Q5 were the lowest and highest Ca intake groups, respectively) to compare their basic background and obstetrics outcome. Multiple logistic regressions were performed to identify the effect of pre-pregnancy Ca intake on HDP, early onset HDP, and late-onset HDP, using Ca intake thresholds of 500, 550, 650, 700, 1000, 1500, and 1500 mg. Results: We found significant differences in maternal background among the Ca intake groups; in particular, there were more participants with low socioeconomic status, indicated by low education level and low household income, and smokers in the lowest Ca intake group. Multiple logistic regression did not show any significant difference with regard to HDP, early onset HDP, and late-onset HDP in each Ca intake threshold. Conclusions: Despite considerable recommendations concerning Ca intake for women of reproductive age, the present study indicates that pre-pregnancy Ca intake was not associated with an increased risk of new-onset hypertension among primiparas during pregnancy. Further studies examining the effect of other pre-pregnancy dietary factors on obstetric outcomes should be considered in the formulation of earlier preventive strategies for primiparas.
The daily diet plays a role in systematic inflammation and may be one of the causes of preterm birth. We aimed to examine the effect of a daily proinflammatory diet before pregnancy on gestational age and birthweight using a large birth cohort in Japan. We used data of singleton pregnancies in the Japan Environment and Children's Study involving live birth from 2011 to 2014 to calculate the dietary inflammatory index. We used individual meals with 30 food parameters from a semiquantitative food frequency questionnaire, which assessed diet intake before pregnancy. Participants were categorized according to the quartile of dietary inflammatory index. A multiple logistic regression model was used to estimate the risk of a proinflammatory diet on preterm birth (PTB) before 37 or 34 weeks and low birthweight (LBW) less than 2,500 or 1,500 g, accounting for maternal age, body mass index before pregnancy, smoking status, education, and household income. After applying our inclusion criteria, 89,329 participants were eligible for the present study. Multiple regression analysis showed that the proinflammatory diet had an increased risk of PTB < 34 weeks (adjusted odds ratio: 1.29, 95% confidence interval [1.07, 1.55]) and <2,500‐g LBW (adjusted odds ratio: 1.08, 95% confidence interval [1.01, 1.16]) compared with the control. In conclusion, a proinflammatory diet before pregnancy was a risk factor for PTB < 34 weeks and LBW < 2,500 g. Therefore, proinflammatory diet needs to be controlled to improve perinatal prognosis.
A high maternal body mass index (BMI) is associated with increased risks of asphyxia-related neonatal morbidity. We evaluated the association between maternal pre-pregnancy BMI and foetal acidosis while accounting for the mode of delivery. Participants from the Japan Environment and Children’s Study with singleton pregnancies after 22 weeks of gestation who gave birth during 2011–2014 were included. The participants (n = 71,799) were categorised into five groups according to the pre-pregnancy BMI: G1 (BMI < 18.5 kg/m2), G2 (18.5 to < 20.0 kg/m2), G3 (20.0 to < 23.0 kg/m2), G4 (23.0 to < 25.0 kg/m2), and G5 (≥ 25.0 kg/m2). Foetal acidosis was defined as umbilical artery pH (UmA-pH) < 7.20 or < 7.10. Multiple logistic regression analyses were used to evaluate the effect of pre-pregnancy BMI on foetal acidosis risk, accounting for the mode of delivery. In Japanese women, pre-pregnancy BMI ≥ 25.0 kg/m2 significantly increased the likelihood of foetal acidosis in newborns delivered vaginally. We found no association between pre-pregnancy BMI and foetal acidosis in newborns delivered via caesarean section. Counselling for body weight control before pregnancy and adequate management and selection of the mode of delivery in pregnant women with a high BMI who are in labour may be essential to avoid foetal acidosis.
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