| BackgroundThe advanced maternal age(AMA)has been considered a significant risk factor associated with adverse pregnancy outcomes.Specific complications of pregnancy including hypertensive disorders of pregnancy(HDP)and abnormal placentations are commonly occur in women with AMA and may cause adverse neonatal outcomes.Over the past decades,the proportion of neonatal births to women with AMA is continuously rising in both developed and developing countries.In China,the rising trend in AMA could be attributed to women's higher education,career development,and universal two-child policy(TCP).It has been estimated that after the universal TCP,an additional 90 million women in China will have a second child.Of these pregnant women,60% are estimated to be older than 35 years(AMA).Therefore,four studies(part 1-4)were performed with the objectives to 1)analyze and verify the impact of AMA on pregnancy outcomes 2)examine the extent to which HDP and abnormal placentation mediate the association between AMA and adverse neonatal outcomes 3)find trends in AMA and adverse pregnancy outcomes over 9 years(2011-2019)4)determine the association of the universal TCP with maternal age and pregnancy outcomes in women with AMA.Material and MethodsA tertiary hospital-based retrospective study was conducted in Wuhan University Renmin Hospital,Hubei Province,China,during the years 2011-2019.In part ?,a chi-square test was used to compare baseline characteristics among groups of maternal age.Multiple binary logistic regression models were conducted to find the association between maternal age and pregnancy outcomes.In part ?,regression based mediation analyses were performed to assess the mediating role of HDP and abnormal placentation between the association of AMA and adverse neonatal outcomes.In part ?,joinpoint regression analyses were used to determine trends in maternal age and adverse pregnancy outcomes from 2011 to 2019.In part IV,to find the potential impact of policy changes;we defined the one-child policy(OCP)period(2011-2013),the partial TCP period(2014-2016),and the universal TCP period as data from 2017 to 2019.Changes in maternal age and pregnancy outcomes in women with AMA were estimated by chi-square tests.Binary logistic regression analyses were used to estimate the association of TCP with the risk of changes in maternal age groups and pregnancy outcomes in women with AMA,with the OCP period being defined as the reference period.Results(1)Women with AMA had significantly higher prevalence of HDP(9.1% vs 5.6%),abnormal placentation(6.5% vs 3.6%),C-section(73.8% vs 53.2%),gestational diabetes mellitus(GDM)(10.8% vs 4.6%),preterm births(25.6% vs 17.8%),perinatal mortality(2.3% vs 1.3%),low birth weight(LBW)(17.6% vs 14.1%),low Apgar score(4.6% vs 3.6%),and macrosomic babies(5.5% vs 4.9%)compared with women aged <30 years.After adjusting for confounding factors(prepregnancy body weight,parity,neonatal gender,maternal education,and occupation),AMA was an independent and statistically significant risk factor associated with increased risk of gestational hypertension(GH)(aOR 1.6;95% CI: 1.2,2.2),preeclampsia(PE)(aOR 1.6;95% CI:1.4,1.9),sever PE(aOR 1.7;95% CI: 1.1,2.6),placenta previa(aOR 1.5;95% CI: 1.3,1.8),GDM(aOR 2.6;95% CI: 2.3,2.9),C-section(aOR 2.4;95% CI: 2.2,2.6),preterm births(aOR 1.4;95%CI: 1.3,1.5),perinatal mortality(aOR 1.5;95% CI: 1.2,2.2),and LBW(aOR 1.2;95% CI: 1.1,1.3).Women aged 30-34 years had higher odds of PE(aOR 1.3;95% CI: 1.2,1.5),placenta previa(aOR 1.2;95% CI: 1.1,1.4),GDM(aOR 1.7;95% CI: 1.5,1.9),diabetes(aOR 1.7;95% CI: 1.1,2.7),C-section(aOR 1.6;95% CI: 1.5,1.6),and fetal macrosomia(aOR 1.3;95% CI: 1.1,1.4)compared with reference age group(<30 years).(2)After adjusting for confounding factors(prepregnancy body weight,parity,neonatal gender,maternal education,and occupation),the indirect effect of AMA on preterm births,perinatal mortality,LBW mediated by HDP was [aOR 4.9(95% CI: 4.1,5.8)],[aOR 2.8(95% CI:1.7,3.8)],and [aOR 5.9(95% CI: 4.9,6.8)],respectively.The indirect effect of AMA on preterm births and LBW mediated by abnormal placentation was [aOR 6.8(95% CI: 5.7,7.9)] and [aOR4.1(95% CI: 3.2,5.1)].About,23%,37%,and 17% of the effect of AMA on preterm births,perinatal mortality,and LBW was mediated by HDP,respectively.Furthermore,abnormal placentation mediates the association between AMA and preterm births by 18% and LBW by 23%.(3)The joinpoint regression analysis revealed that trends in AMA increased by 75%[AAPC 10.1%(95% CI: 9.4,10.9)] during the study period.Trends in age-standardized rates of HDP increased by 2.7% [AAPC 2.5%(95% CI: 1.1,3.9)],abnormal placentation by 21% [AAPC1.2 %(95% CI: 1.1,2.1)],GDM by 250% [AAPC 46.0%(95% CI:-2.7,119.0)],perinatal mortality by 53.5% [AAPC 13.7%(95% CI:-32.7,92.2)],intrauterine growth restriction(IUGR)by 105% [AAPC 12.0%(95% CI:-19.7,56.4)],and fetal macrosomia by 22.7% [AAPC 2.6 %(95% CI:-10.0,16.9).However,the trend of age-standardized rates in C-section decreased by 6.5%[AAPC-1.0%(95% CI:-2.4,0.5)],preterm births by 21% [AAPC-3.4 %(95% CI:-7.8,-1.2)],LBW by 28.2% [ AAPC-4.7%(95% CI:-6.0,-3.3)],low ponderal index(LPI)by 78.5% [AAPC-15.2 %(95% CI:-43.1,26.4)],low Apgar score by 53.2% [AAPC-7.6 %(95% CI:-25.0,13.8)],fetal distress by 63.3% [AAPC-14.0%(95% CI:-17.8,-10.0)],and congenital defects by 51.7%[AAPC-7.3%(95% CI:-22.9,11.5)] during 2011-2019.(4)The proportion of neonatal births to women with AMA increased by 68.8% from 12.5%in OCP period to 21.1% in universal TCP period.After adjusting for confounding factors(prepregnancy body weight,parity,neonatal gender,maternal education,and occupation),the risk of AMA significantly increased [aOR 1.76(95% CI: 1.60,1.93)] in universal TCP period compared with the OCP period.Among adverse pregnancy outcomes in women with AMA,the proportion of preterm births(29.4% to 24.1%),LBW(20.9% to 15.9%),low Apgar score(4.8%to 3.6%),fetal distress(4.5% to 2.2%),HDP(11.5% to 9.2%),and C-section(73.5% to 71.8%)were significantly(p<0.05)decreased from the OCP period to the universal TCP period.However,the proportion of IUGR(0.2% to 0.7%)and GDM(1.7% to 15.6%)were significantly(p<0.05)increased over the policy changes.Compared with the OCP period,after adjusting for confounding factors(prepregnancy body weight,parity,neonatal gender,maternal education,and occupation),the risk of GDM increased [aOR 10.91(95% CI: 6.05,19.67)] in women with AMA in the TCP period.ConclusionIn conclusion,women with AMA had higher odds of adverse pregnancy outcomes.HDP and abnormal placentation partially mediate the association between AMA and adverse neonatal outcomes.Between 2011 and 2019,trend in AMA is increased.Among adverse pregnancy outcomes,increasing trends in age-standardized rates of HDP,abnormal placentation,GDM,perinatal mortality,IUGR,and fetal macrosomia and decreasing trends in age-standardized rates of C-section,preterm births,LBW,LPI,low Apgar score,fetal distress,and congenital defects were observed.The risk of AMA significantly increased from the OCP period to the universal TCP period.In women with AMA,the proportion of preterm births,LBW,and HDP significantly decreased and the proportion of fetal macrosomia,IUGR,and GDM significantly increased over the policy changes.These findings will help maternal health care givers to educate women about the consequences of delayed childbearing,and provide evidence-based knowledge to support women about their procreation choices.This study would be also useful for health policy makers to design planning and strategies to prevent increasing trends in AMA and adverse pregnancy outcomes and implement adequate health care systems and intervention programs in Hubei,China. |
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