Impact of extreme maternal age on neonatal outcomes

INTRODUCTION

Pregnancies at extreme ages of reproductive life are considered at risk of unfavourable outcome for both mother and neonate.¹ Adverse neonatal outcomes reported in the literature include neonatal death, preterm birth, low birthweight, low Apgar score, transfer to a neonatal intensive care unit, fetal macrosomia, and congenital malformation.^2-5 However, nearly 16 million adolescents aged of 15-19 and one million adolescents under 15 years of age still give birth each year.⁶ More than 90% of these births take place in developing countries.⁷ In Madagascar, 20 to 30% of adolescents become mothers before reaching age of 18.⁸ On the other hand, pregnancy after 40 years remains a topical issue among Malagasy women.⁸ The hospital frequency of pregnancies after 40 years was 0.61%.⁹ The objective of this work was to determine the neonatal risks associated with extreme maternal ages.

METHODS

This was a retrospective cohort study covering the period from 1 January to 31 December 2018. This study was based on a study of neonate’s medical records. The study was conducted at neonatology department of Befelatanana Maternity, which is a reference maternity in the capital of Madagascar. The hospital has an average of 7.000 deliveries annually.

Study population was neonates born at the Befelatanana maternity during the study period. According to maternal age, three groups of neonates were included. Group 1 was composed of neonates whose mother's age is less than 18 years. Group 2 was composed of neonates whose mothers were aged 40 and over. Group 3 (control group) was made up of neonates whose mothers were aged 20-30. Exclusion criteria were neonates from multiple pregnancy and/or discharged against medical advice and/or with incomplete medical records. The sampling was exhaustive for groups 1, 2 and 3. Neonates in group 3 were born on the same day as those in group 1 or 2. All data were collected from medical records. The variables studied were maternal, obstetrical and neonatal variables.

Data were analyzed using Epi info 7® software. The relative risk (RR) was calculated with a 95% confidence interval (95% CI) to determine the neonatal risks of pregnancies at extreme ages. Chi square test and Fischer exact test were used for the comparison of proportions. A two-sided p<0.05 was considered statistically significant. Given the retrospective design of this study, only medical records were reviewed. There was no direct interaction between the investigator and people whose medical records targeted by the study. This study respected the ethical principles of the declaration of Helsinki. The study obtained the authorization of the Management of the hospital and approval of the scientific committee of the Befelatanana maternity. Patient anonymity was respected during data collection and analysis.

RESULTS

During the study period, there was 834 births at extreme maternal ages. Only 799 of them were included of which 64.7% (N=517) among mothers under 18 and 35.3% (N=282) among mothers aged 40 and more. Thirty-five neonates were excluded whose 19 from multiple pregnancy, 16 with an incomplete medical record. The mean age of teenage mothers was 16.5±0.8 years with extremes of 12 and 17 years. For mothers aged of 40 and more, the mean age was 41.7±2.1 years with extremes of 40 and 51 years.

Neonates from teenage mothers and neonates from mothers aged of 40 years and more were separately compared to 519 neonates from mothers aged 20-30. Almost all teenage mothers (96.9%) were primipara. Among mothers at advanced ages, 9.2% were primipara. The proportion of mothers who did not perform any prenatal follow-up was significantly higher among mothers at extreme ages. The proportions of mothers at the two extremes of age having performed at least eight prenatal consultations (as recommended by World Health Organization) were significantly lower than in the control group. Mothers at extreme ages were experimenting more cesarean section with a rate of 35.2% among teenage mothers and 49.6% among elderly mothers (Table 1). The most frequent pathology in the two extremes of age was arterial hypertension which affected 19.9% of adolescent mothers and 46.8% of older mothers.

ND = Not defined, * Significant value.

The proportion of mothers with eclampsia was higher in adolescent parturients. In contrast, chronic hypertension and pre-eclampsia were more common among mothers aged 40 and over (Table 2). Neonates from adolescent mothers were hospitalized in Neonatology in 58.1% of cases, and those from mothers aged 40 and over in 67% of cases. In terms of neonatal deaths, 44 deaths (8.5%) were deplored in neonates of adolescent mothers and 25 deaths (8.9%) in those of mothers at advanced age. Maternal age below 18 years was a risk factor for APGAR index below 7 at the 5th minute, preterm birth, low birthweight and admission to Neonatology (Table 3). The neonatal risks of pregnancy after the age of 40 were fetal death in utero, low birthweight, preterm birth and admission to neonatology (Table 4).

DISCUSSION

In this study, pregnant women at extreme ages have a higher risk of giving birth to low birthweight neonate as found in other studies.^10,11 Some biological hypotheses have been put forward to explain these findings. A pregnant teenager, still in the growth phase, could compete for nutrients with the fetus.¹⁶ Hayward et al pointed out that poor growth in adolescent, potentially due to poor nutritional status, could impact placental function and increase the risk of low birthweight.¹⁷ Likewise, they confirmed the hypothesis that the activity of placental nutrient transporter is affected by young age.¹⁷ Maternal age above or equal to 40 years was a risk factor for having a low birthweight neonates in our series, as found in a Thai study.¹² This association could be due to changes in the uterine vasculature.¹³ Placental abnormalities observed with low birthweight reflected reduced blood flow to the placenta.¹⁴ Lean et al showed that placental dysfunction would explain the increased risk of fetal growth retardation in women of advanced age.¹⁵ Aras also put forward the hypothesis of biological aging of maternal tissues and systems or cumulative effects of associated defects.¹⁶ The risk of premature delivery increased among adolescent mothers and among mothers aged of 40 and older. This association between preterm delivery and the young age of the mother was found in another study.^11,18 Other factors such as the absence of prenatal consultations and the occurrence of preeclampsia were also associated with preterm delivery.¹⁸

Chen et al hypothesized that immaturity of the uterine or cervical vasculature during teenage pregnancy may increase the risk of subclinical infection and production of prostaglandins and thus lead to an increased risk of preterm delivery.² The association of advanced maternal age with preterm birth was also reported in other studies.^19-21 Family planning, including contraception remains a good strategy in preventing pregnancy at these high-risk ages. Nevertheless, in case of pregnancy, prenatal follow-up should be regular, rigorous and of high quality. Similarly, childbirth should take place in a referral hospital. Pregnancy in adolescence was a risk factor for low Apgar score and even perinatal asphyxia, as reported in other studies.^2,11 In this work, the most frequent pathology in adolescent was arterial hypertension (19.9%). Eclampsia, a major neurological complication of preeclampsia, affected adolescents more as reported by other authors.^22,23 The link between arterial hypertension and perinatal asphyxia could be explained biologically by uteroplacental insufficiency leading to a reduction in blood flow, loss of placental integrity and damage to endothelial cells which may predispose the fetus to growth retardation and perinatal anoxia.²³ In addition to vascular changes, seizures during eclampsia and anticonvulsant drugs could also contribute to a lower Apgar score at birth.²⁵ Moreover, 96.9% of adolescent mothers were primipara in our series. An association between primiparity and perinatal asphyxia has often been reported in the literature.^26-28 Primipara adolescent mothers are more prone to incorrect presentations, obstructed labor and therefore to a higher risk of perinatal asphyxia.²⁷ The duration of the first and second stage of labor could also be important in primipara women.²⁹ Furthermore, primipara women are sometimes unaware of the demands of pregnancy and often lack routine prenatal care.²⁶ Pregnancy at the extreme ages of reproductive life increased the risk of admission to Neonatology. The risk was increased 2.64 times in neonates of teenage mothers and 3.06 times in neonates of elderly mothers compared to the control group. This hospitalization in Neonatology was generally the consequence of maternal complications during pregnancy and childbirth such as eclampsia, pre-eclampsia, haemorrhages during pregnancy, obstructed labor and infectious pathologies. In our series, extreme maternal age did not significantly increase the risk of neonatal death, contrary to what is reported in the literature.^2,10,20 According to Tebeu et al poverty, malnutrition, inadequate prenatal care and infections are common in developing countries and may be co-factors of stillbirths.³⁰ The fetal risk of in utero death was three times higher in mothers aged 40 and over compared to the control group, corroborating the findings of other authors.^31,32 Several reasons such as arterial hypertension, diabetes, obesity, risk of placenta previa and fetal malformations would explain this predisposition of the elderly woman to fetal death in utero. Adequate management of pathologies during pregnancy, early detection of malformations could thus improve prognosis of these pregnancies in women at advanced ages. Nevertheless, prevention of pregnancies at these risky ages would be more judicious. However, this study had some limitations. Its retrospective nature meant that certain information concerning the patients was missing. Furthermore, the results of the study remain valid only for the Befelatanana maternity. Therefore, a multicenter study should be conducted in order to have a unanimously accepted result.

CONCLUSION

Pregnancy at the extreme ages of reproductive life increase risk of adverse neonatal outcomes. Follow-up of these high-risk pregnancies deserves more attention and must be more rigorous in order to detect and anticipate possible complications.

ACKNOWLEDGEMENTS

The authors would like to thank technical staff and health workers of Befelatanana maternity for their support, cooperation and assistance in carrying out this study this study.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: The study was approved by the Institutional Ethics Committee

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